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class="vector-toc-numb">2</span> <span>Mechanism of action</span> </div> </a> <ul id="toc-Mechanism_of_action-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-History_in_hairy_cell_leukemia" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#History_in_hairy_cell_leukemia"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>History in hairy cell leukemia</span> </div> </a> <ul id="toc-History_in_hairy_cell_leukemia-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Safety_profile_of_cladribine_in_hairy_cell_leukemia" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Safety_profile_of_cladribine_in_hairy_cell_leukemia"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>Safety profile of cladribine in hairy cell leukemia</span> </div> </a> <ul id="toc-Safety_profile_of_cladribine_in_hairy_cell_leukemia-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-History_in_multiple_sclerosis" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#History_in_multiple_sclerosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>History in multiple sclerosis</span> </div> </a> <ul id="toc-History_in_multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Use_in_multiple_sclerosis" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Use_in_multiple_sclerosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>Use in multiple sclerosis</span> </div> </a> <ul id="toc-Use_in_multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Efficacy_of_cladribine_tablets_in_multiple_sclerosis" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Efficacy_of_cladribine_tablets_in_multiple_sclerosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>Efficacy of cladribine tablets in multiple sclerosis</span> </div> </a> <ul id="toc-Efficacy_of_cladribine_tablets_in_multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Safety_profile_of_cladribine_tablets_in_multiple_sclerosis" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Safety_profile_of_cladribine_tablets_in_multiple_sclerosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">8</span> <span>Safety profile of cladribine tablets in multiple sclerosis</span> </div> </a> <ul id="toc-Safety_profile_of_cladribine_tablets_in_multiple_sclerosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Research" class="vector-toc-list-item vector-toc-level-1 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href="https://cy.wikipedia.org/wiki/Cladribin" title="Cladribin – Welsh" lang="cy" hreflang="cy" data-title="Cladribin" data-language-autonym="Cymraeg" data-language-local-name="Welsh" class="interlanguage-link-target"><span>Cymraeg</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Cladribin" title="Cladribin – German" lang="de" hreflang="de" data-title="Cladribin" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Cladribina" title="Cladribina – Spanish" lang="es" hreflang="es" data-title="Cladribina" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%DA%A9%D9%84%D8%A7%D8%AF%D8%B1%DB%8C%D8%A8%DB%8C%D9%86" title="کلادریبین – Persian" lang="fa" hreflang="fa" data-title="کلادریبین" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Cladribine" title="Cladribine – French" lang="fr" hreflang="fr" data-title="Cladribine" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Cladribina" title="Cladribina – Italian" lang="it" hreflang="it" data-title="Cladribina" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E3%82%AF%E3%83%A9%E3%83%89%E3%83%AA%E3%83%93%E3%83%B3" title="クラドリビン – Japanese" lang="ja" hreflang="ja" data-title="クラドリビン" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-or mw-list-item"><a href="https://or.wikipedia.org/wiki/%E0%AC%95%E0%AD%8D%E0%AC%B2%E0%AC%BE%E0%AC%A1%E0%AD%8D%E0%AC%B0%E0%AC%BF%E0%AC%AC%E0%AC%BE%E0%AC%87%E0%AC%A8" title="କ୍ଲାଡ୍ରିବାଇନ – Odia" lang="or" hreflang="or" data-title="କ୍ଲାଡ୍ରିବାଇନ" data-language-autonym="ଓଡ଼ିଆ" data-language-local-name="Odia" class="interlanguage-link-target"><span>ଓଡ଼ିଆ</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Kladrybina" title="Kladrybina – Polish" lang="pl" hreflang="pl" data-title="Kladrybina" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Cladribin%C4%83" title="Cladribină – Romanian" lang="ro" hreflang="ro" data-title="Cladribină" data-language-autonym="Română" data-language-local-name="Romanian" class="interlanguage-link-target"><span>Română</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%9A%D0%BB%D0%B0%D0%B4%D1%80%D0%B8%D0%B1%D0%B8%D0%BD" title="Кладрибин – Russian" lang="ru" hreflang="ru" data-title="Кладрибин" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/Kladribin" title="Kladribin – Serbian" lang="sr" hreflang="sr" data-title="Kladribin" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target"><span>Српски / srpski</span></a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Kladribin" title="Kladribin – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Kladribin" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target"><span>Srpskohrvatski / српскохрватски</span></a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%9A%D0%BB%D0%B0%D0%B4%D1%80%D0%B8%D0%B1%D1%96%D0%BD" title="Кладрибін – Ukrainian" lang="uk" hreflang="uk" data-title="Кладрибін" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target"><span>Українська</span></a></li><li class="interlanguage-link interwiki-vi mw-list-item"><a href="https://vi.wikipedia.org/wiki/Cladribine" title="Cladribine – Vietnamese" lang="vi" hreflang="vi" data-title="Cladribine" 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<div class="vector-body-before-content"> <div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Pharmaceutical drug</div> <p class="mw-empty-elt"> </p> <div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Pharmaceutical compound</div> <style data-mw-deduplicate="TemplateStyles:r1269284339">@media screen{html.skin-theme-clientpref-night .mw-parser-output .dark_mode_safe img{background-color:var(--background-color-inverted,#f8f9fa)}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .dark_mode_safe img{background-color:var(--background-color-inverted,#f8f9fa)}}</style> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox" style="border-spacing:2px;"><caption class="infobox-title"><span title="International nonproprietary name (INN): Cladribine">Cladribine</span></caption><tbody><tr><td colspan="2" class="infobox-image"><span class="skin-invert-image" typeof="mw:File"><a href="/wiki/File:Cladribine.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/7a/Cladribine.svg/200px-Cladribine.svg.png" decoding="async" width="200" height="177" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/7a/Cladribine.svg/300px-Cladribine.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/7a/Cladribine.svg/400px-Cladribine.svg.png 2x" data-file-width="512" data-file-height="454" /></a></span></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd;color:inherit;">Clinical data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Drug_nomenclature#Trade_names" title="Drug nomenclature">Trade names</a></th><td class="infobox-data">Leustatin, Mavenclad, others<sup id="cite_ref-drugs.comINT_1-0" class="reference"><a href="#cite_note-drugs.comINT-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;">Other names</th><td class="infobox-data">2-Chlorodeoxyadenosine; 2-Chloro-2'-deoxyadenosine; 2-CdA</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/American_Society_of_Health-System_Pharmacists" title="American Society of Health-System Pharmacists">AHFS</a>/<a href="/wiki/Drugs.com" title="Drugs.com">Drugs.com</a></th><td class="infobox-data"><span title="www.drugs.com"><a rel="nofollow" class="external text" href="https://www.drugs.com/monograph/cladribine.html">Monograph</a></span></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/MedlinePlus" title="MedlinePlus">MedlinePlus</a></th><td class="infobox-data"><span title="medlineplus.gov"><a rel="nofollow" class="external text" href="https://medlineplus.gov/druginfo/meds/a693015.html">a693015</a></span></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Regulation_of_therapeutic_goods" title="Regulation of therapeutic goods">License data</a></th><td class="infobox-data"><style data-mw-deduplicate="TemplateStyles:r1126788409">.mw-parser-output .plainlist ol,.mw-parser-output .plainlist ul{line-height:inherit;list-style:none;margin:0;padding:0}.mw-parser-output .plainlist ol li,.mw-parser-output .plainlist ul li{margin-bottom:0}</style><div class="plainlist"> <ul><li><small><abbr class="country-name" title="United States">US</abbr></small> <a href="/wiki/DailyMed" title="DailyMed">DailyMed</a>: <span title="dailymed.nlm.nih.gov"><a rel="nofollow" class="external text" href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Cladribine">Cladribine</a></span></li></ul></div> </td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Pregnancy_category" title="Pregnancy category">Pregnancy<br />category</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li><small><abbr class="country-name" title="Australia">AU</abbr>:</small> D</li> <li class="mw-empty-elt"></li></ul> </div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Route_of_administration" title="Route of administration">Routes of<br />administration</a></th><td class="infobox-data"><a href="/wiki/Intravenous" class="mw-redirect" title="Intravenous">Intravenous</a>, <a href="/wiki/Subcutaneous_injection" class="mw-redirect" title="Subcutaneous injection">subcutaneous</a> (liquid), <a href="/wiki/By_mouth" class="mw-redirect" title="By mouth">by mouth</a> (tablet)</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">ATC code</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><a href="/wiki/ATC_code_L01" title="ATC code L01">L01BB04</a> (<span title="www.whocc.no"><a rel="nofollow" class="external text" href="https://www.whocc.no/atc_ddd_index/?code=L01BB04">WHO</a></span>) (<a href="/wiki/Parenteral" class="mw-redirect" title="Parenteral">parenteral</a>)<br /><a href="/wiki/ATC_code_L04" title="ATC code L04">L04AA40</a> (<span title="www.whocc.no"><a rel="nofollow" class="external text" href="https://www.whocc.no/atc_ddd_index/?code=L04AA40">WHO</a></span>) (<a href="/wiki/Mouth" title="Mouth">oral</a> for <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>)</li></ul></div></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd;color:inherit;">Legal status</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Regulation_of_therapeutic_goods" title="Regulation of therapeutic goods">Legal status</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li><small><abbr class="country-name" title="Australia">AU</abbr>:</small> <a href="/wiki/Standard_for_the_Uniform_Scheduling_of_Medicines_and_Poisons#Schedule_4" title="Standard for the Uniform Scheduling of Medicines and Poisons">S4</a> (Prescription only)</li> <li><small><abbr class="country-name" title="Canada">CA</abbr></small>: <a href="/wiki/Prescription_drug" title="Prescription drug"> ℞-only</a><sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li> <li><small><abbr class="country-name" title="United Kingdom">UK</abbr>:</small> <a href="/wiki/Prescription_drug" title="Prescription drug">POM</a> (Prescription only)</li> <li><small><abbr class="country-name" title="United States">US</abbr>:</small> <a href="/wiki/Boxed_warning" title="Boxed warning"><span style="border:thin solid black;">WARNING</span></a><sup id="cite_ref-FDA-AllBoxedWarnings_2-0" class="reference"><a href="#cite_note-FDA-AllBoxedWarnings-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup>Rx-only</li> <li><small><abbr class="country-name" title="European Union">EU</abbr>:</small> Rx-only<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></li></ul></div> </td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd;color:inherit;"><a href="/wiki/Pharmacokinetics" title="Pharmacokinetics">Pharmacokinetic</a> data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Bioavailability" title="Bioavailability">Bioavailability</a></th><td class="infobox-data">100% (<a href="/wiki/Intravenous" class="mw-redirect" title="Intravenous">i.v.</a>); 37 to 51% (<a href="/wiki/Mouth" title="Mouth">orally</a>)<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Plasma_protein_binding" title="Plasma protein binding">Protein binding</a></th><td class="infobox-data">25% (range 5-50%);<sup id="cite_ref-TGA_6-0" class="reference"><a href="#cite_note-TGA-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> up to 20% (orally) <sup id="cite_ref-Giovannoni_Neurotherapeutics_7-0" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Drug_metabolism" title="Drug metabolism">Metabolism</a></th><td class="infobox-data">Mostly via <a href="/wiki/Intracellular" class="mw-redirect" title="Intracellular">intracellular</a> <a href="/wiki/Kinase" title="Kinase">kinases</a>; 15-18% is excreted unchanged.<sup id="cite_ref-TGA_6-3" class="reference"><a href="#cite_note-TGA-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> <p>Intravenous and subcutaneous bolus injection: 15-18% is excreted unchanged </p> After oral administration, 25% (±21%) of dose is excreted unchanged in urine and 3.8% as a metabolite.<sup id="cite_ref-Giovannoni_Neurotherapeutics_7-1" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Biological_half-life" title="Biological half-life">Elimination <span class="nowrap">half-life</span></a></th><td class="infobox-data">Approximately 10 hours after both intravenous infusion and subcutaneous bolus injection ranging from 5.6 to 7.6 hours<sup id="cite_ref-TGA_6-1" class="reference"><a href="#cite_note-TGA-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> and 18.4 to 19.7 hours after oral administration, indicative of different elimination phases.</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Excretion" title="Excretion">Excretion</a></th><td class="infobox-data">Urinary<sup id="cite_ref-TGA_6-2" class="reference"><a href="#cite_note-TGA-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd;color:inherit;">Identifiers</th></tr><tr><td colspan="2" class="infobox-full-data"><div class="collapsible-list mw-collapsible mw-collapsed" style="text-align: left;"> <div style="line-height: 1.6em; font-weight: bold;"><div><a href="/wiki/IUPAC_nomenclature_of_chemistry" title="IUPAC nomenclature of chemistry">IUPAC name</a></div></div> <ul class="mw-collapsible-content" style="margin-top: 0; margin-bottom: 0; line-height: inherit; list-style: none; margin-left: 0; word-break:break-all; text-align:left; padding-left:1.5em; text-indent:-1.5em;"><li style="line-height: inherit; margin: 0"><div style="font-size: 97%;">5-(6-Amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol</div></li></ul> </div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/CAS_Registry_Number" title="CAS Registry Number">CAS Number</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="commonchemistry.cas.org"><a rel="nofollow" class="external text" href="https://commonchemistry.cas.org/detail?cas_rn=4291-63-8">4291-63-8</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/PubChem#CID" title="PubChem">PubChem</a> <span style="font-weight:normal"><abbr title="Compound ID">CID</abbr></span></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="pubchem.ncbi.nlm.nih.gov"><a rel="nofollow" class="external text" href="https://pubchem.ncbi.nlm.nih.gov/compound/20279">20279</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Guide_to_Pharmacology" title="Guide to Pharmacology">IUPHAR/BPS</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.guidetopharmacology.org"><a rel="nofollow" class="external text" href="https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4799">4799</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/DrugBank" title="DrugBank">DrugBank</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.drugbank.ca"><a rel="nofollow" class="external text" href="https://www.drugbank.ca/drugs/DB00242">DB00242</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/ChemSpider" title="ChemSpider">ChemSpider</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.chemspider.com"><a rel="nofollow" class="external text" href="https://www.chemspider.com/Chemical-Structure.19105.html">19105</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Unique_Ingredient_Identifier" title="Unique Ingredient Identifier">UNII</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="precision.fda.gov"><a rel="nofollow" class="external text" href="https://precision.fda.gov/uniisearch/srs/unii/47M74X9YT5">47M74X9YT5</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/KEGG" title="KEGG">KEGG</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.kegg.jp"><a rel="nofollow" class="external text" href="https://www.kegg.jp/entry/D01370">D01370</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/ChEBI" title="ChEBI">ChEBI</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.ebi.ac.uk"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:567361">CHEBI:567361</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/ChEMBL" title="ChEMBL">ChEMBL</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.ebi.ac.uk"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/chembl/explore/compound/ChEMBL1619">ChEMBL1619</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/CompTox_Chemicals_Dashboard" title="CompTox Chemicals Dashboard">CompTox Dashboard</a> <span style="font-weight:normal">(<abbr title="U.S. Environmental Protection Agency">EPA</abbr>)</span></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="comptox.epa.gov"><a rel="nofollow" class="external text" href="https://comptox.epa.gov/dashboard/chemical/details/DTXSID8022828">DTXSID8022828</a> <span class="mw-valign-text-top noprint" typeof="mw:File/Frameless"><a href="https://www.wikidata.org/wiki/Q414030#P3117" title="Edit this at Wikidata"><img alt="Edit this at Wikidata" src="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/10px-OOjs_UI_icon_edit-ltr-progressive.svg.png" decoding="async" width="10" height="10" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/15px-OOjs_UI_icon_edit-ltr-progressive.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png 2x" data-file-width="20" data-file-height="20" /></a></span></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/ECHA_InfoCard" class="mw-redirect" title="ECHA InfoCard"><span title="echa.europa.eu">ECHA InfoCard</span></a></th><td class="infobox-data"><a rel="nofollow" class="external text" href="https://echa.europa.eu/substance-information/-/substanceinfo/100.164.726">100.164.726</a> <span class="mw-valign-text-top noprint" typeof="mw:File/Frameless"><a href="https://www.wikidata.org/wiki/Q414030#P2566" title="Edit this at Wikidata"><img alt="Edit this at Wikidata" src="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/10px-OOjs_UI_icon_edit-ltr-progressive.svg.png" decoding="async" width="10" height="10" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/15px-OOjs_UI_icon_edit-ltr-progressive.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png 2x" data-file-width="20" data-file-height="20" /></a></span></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd;color:inherit;">Chemical and physical data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Chemical_formula" title="Chemical formula">Formula</a></th><td class="infobox-data"><span title="Carbon">C</span><sub>10</sub><span title="Hydrogen">H</span><sub>12</sub><span title="Chlorine">Cl</span><span title="Nitrogen">N</span><sub>5</sub><span title="Oxygen">O</span><sub>3</sub></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Molar_mass" title="Molar mass">Molar mass</a></th><td class="infobox-data"><span class="nowrap"><span data-sort-value="7002285690000000000♠"></span>285.69</span> g·mol<sup>−1</sup></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;">3D model (<a href="/wiki/JSmol" class="mw-redirect" title="JSmol">JSmol</a>)</th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="chemapps.stolaf.edu (3D interactive model)"><a rel="nofollow" class="external text" href="https://chemapps.stolaf.edu/jmol/jmol.php?model=Clc1nc%28c2ncn%28c2n1%29%5BC%40%40H%5D3O%5BC%40%40H%5D%28%5BC%40%40H%5D%28O%29C3%29CO%29N">Interactive image</a></span></li></ul></div></td></tr><tr><td colspan="2" class="infobox-full-data"><div class="collapsible-list mw-collapsible mw-collapsed" style="text-align: left;"> <div style="line-height: 1.6em; font-weight: bold;"><div><a href="/wiki/Simplified_molecular-input_line-entry_system" class="mw-redirect" title="Simplified molecular-input line-entry system">SMILES</a></div></div> <ul class="mw-collapsible-content" style="margin-top: 0; margin-bottom: 0; line-height: inherit; list-style: none; margin-left: 0; word-break:break-all;"><li style="line-height: inherit; margin: 0"><div style="word-wrap:break-word; text-indent:-1.5em; text-align:left; padding-left:1.5em; font-size:97%; line-height:120%;">Clc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)C3)CO)N</div></li></ul> </div></td></tr><tr><td colspan="2" class="infobox-full-data"><div class="collapsible-list mw-collapsible mw-collapsed" style="text-align: left;"> <div style="line-height: 1.6em; font-weight: bold;"><div><a href="/wiki/International_Chemical_Identifier" title="International Chemical Identifier">InChI</a></div></div> <ul class="mw-collapsible-content" style="margin-top: 0; margin-bottom: 0; line-height: inherit; list-style: none; margin-left: 0; word-break:break-all;"><li style="line-height: inherit; margin: 0"><div style="word-wrap:break-word; text-indent:-1.5em; text-align:left; padding-left:1.5em; font-size:97%; line-height:120%;">InChI=1S/C10H12ClN5O3/c11-10-14-8(12)7-9(15-10)16(3-13-7)6-1-4(18)5(2-17)19-6/h3-6,17-18H,1-2H2,(H2,12,14,15)/t4-,5+,6+/m0/s1<sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></div></li><li style="line-height: inherit; margin: 0"><div style="word-wrap:break-word; text-indent:-1.5em; text-align:left; padding-left:1.5em; font-size:97%; line-height:120%;">Key:PTOAARAWEBMLNO-KVQBGUIXSA-N<sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></div></li></ul> </div></td></tr><tr><td colspan="2" class="infobox-below"><style data-mw-deduplicate="TemplateStyles:r886047488">.mw-parser-output .nobold{font-weight:normal}</style><span class="nobold">  <span class="reflink plainlinks nourlexpansion"><a class="external text" href="https://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=460040776&page2=Cladribine">(verify)</a></span></span></td></tr></tbody></table> <p><b>Cladribine</b>, sold under the brand name <b>Leustatin</b>, among others, is a medication used to treat <a href="/wiki/Hairy_cell_leukemia" title="Hairy cell leukemia">hairy cell leukemia</a> (formally named leukemic reticuloendotheliosis) and <a href="/wiki/B-cell_chronic_lymphocytic_leukemia" class="mw-redirect" title="B-cell chronic lymphocytic leukemia">B-cell chronic lymphocytic leukemia</a>.<sup id="cite_ref-EMA_8-0" class="reference"><a href="#cite_note-EMA-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-EMC_9-0" class="reference"><a href="#cite_note-EMC-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Cladribine, sold under the brand name <b>Mavenclad</b>, is used for the treatment of adults with highly active forms of <a href="/wiki/Relapsing-remitting_multiple_sclerosis" class="mw-redirect" title="Relapsing-remitting multiple sclerosis">relapsing-remitting multiple sclerosis</a>.<sup id="cite_ref-EMA_2021_10-0" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>Cladribine is a purine analogue that selectively targets and suppresses <a href="/wiki/Lymphocytes" class="mw-redirect" title="Lymphocytes">lymphocytes</a> implicated in the underlying pathogenesis of <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a> and B-cell leukaemia.<sup id="cite_ref-Leist_and_Weissert_11-0" class="reference"><a href="#cite_note-Leist_and_Weissert-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Giovannoni_Neurotherapeutics_7-2" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid24652320_12-0" class="reference"><a href="#cite_note-pmid24652320-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Chemically, it mimics the <a href="/wiki/Nucleoside" title="Nucleoside">nucleoside</a> <a href="/wiki/Deoxyadenosine" title="Deoxyadenosine">deoxyadenosine</a>. However, unlike deoxyadenosine, it is relatively resistant to breakdown by the enzyme <a href="/wiki/Adenosine_deaminase" title="Adenosine deaminase">adenosine deaminase</a>, which causes it to accumulate in targeted cells and interfere with the cell's ability to process DNA.<sup id="cite_ref-Giovannoni_Neurotherapeutics_7-3" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Cladribine is taken up by cells via transporter proteins. Once inside a cell, cladribine undergoes phosphorylation by the enzyme <a href="/wiki/Deoxycytidine_kinase" title="Deoxycytidine kinase">deoxycytidine kinase</a> (DCK) to produce mononucleotide 2-chlorodeoxyadenosine 5’monophosphate (2-CdAMP), which is subsequently phosphorylated to the triphosphorylated active compound 2-chlorodeoxyadenosine 5’triphosphate (2-CdATP). Activated cladribine is incorporated into cellular DNA, which triggers <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>. Accumulation of cladribine into cells is dependent on the ratio of DCK and <a href="/wiki/5%27-nucleotidase" title="5'-nucleotidase">5'-nucleotidase</a> (5’-NT), which breaks down and inactivates the compound. This ratio differs between cell types, with high levels in T and B lymphocytes, resulting in selective targeting of these cells. In contrast, DCK:5'NT is relatively low in other cell types, thus sparing numerous non-haematological cells.<sup id="cite_ref-Leist_and_Weissert_11-1" class="reference"><a href="#cite_note-Leist_and_Weissert-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Giovannoni_Neurotherapeutics_7-4" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p><p>It is on the <a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">World Health Organization's List of Essential Medicines</a>.<sup id="cite_ref-WHO23rd_13-0" class="reference"><a href="#cite_note-WHO23rd-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Medical_uses">Medical uses</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=1" title="Edit section: Medical uses"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Cladribine is used as a first- and second-line treatment for symptomatic hairy cell leukemia and for B-cell chronic lymphocytic leukaemia, and is administered by intravenous or subcutaneous infusion.<sup id="cite_ref-EMC_9-1" class="reference"><a href="#cite_note-EMC-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Label_14-0" class="reference"><a href="#cite_note-Label-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Some investigators have used the parenteral formulation orally to treat patients with hairy cell leukemia. About 37–51% of oral cladribine is bioavailable orally.<sup id="cite_ref-Giovannoni_Neurotherapeutics_7-5" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> It is used, often in combination with other cytotoxic agents, to treat various kinds of <a href="/wiki/Histiocytosis" title="Histiocytosis">histiocytosis</a>, including <a href="/wiki/Erdheim%E2%80%93Chester_disease" title="Erdheim–Chester disease">Erdheim–Chester disease</a><sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/Langerhans_cell_histiocytosis" title="Langerhans cell histiocytosis">Langerhans cell histiocytosis</a>.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p><p>Following EMA approval of cladribine tablets for the treatment of adult patients with highly active relapsing-remitting multiple sclerosis in 2017, as of July 2020, cladribine tablets have gained marketing authorisation in over 75 countries.<sup id="cite_ref-Rammohan_2020_17-0" class="reference"><a href="#cite_note-Rammohan_2020-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> In 2019, cladribine tablets were approved by the FDA for the treatment of relapsing forms of multiple sclerosis, to include <a href="/wiki/Multiple_sclerosis#Types_and_variants" title="Multiple sclerosis">relapsing-remitting disease and active secondary progressive</a> disease, in adult patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis.<sup id="cite_ref-Rammohan_2020_17-1" class="reference"><a href="#cite_note-Rammohan_2020-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid32256946_18-0" class="reference"><a href="#cite_note-pmid32256946-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> </p><p>Cladribine may cause foetal harm when administered to a pregnant woman and is listed by the FDA as <a href="/wiki/US_pregnancy_category_B" class="mw-redirect" title="US pregnancy category B">pregnancy category D</a>; safety and efficacy in children has not been established.<sup id="cite_ref-Label_14-1" class="reference"><a href="#cite_note-Label-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Mechanism_of_action">Mechanism of action</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=2" title="Edit section: Mechanism of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>As a purine analogue, cladribine is taken up into rapidly proliferating cells, including B and T lymphocytes, to be incorporated into DNA synthesis. Chemically, it mimics nucleoside adenosine; however, unlike adenosine, cladribine has a chlorine molecule at position 2, which renders it partially resistant to breakdown by adenosine deaminase. This causes it to accumulate in cells and interfere with the targeted cell's ability to process DNA.<sup id="cite_ref-Giovannoni_Neurotherapeutics_7-6" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Leist_and_Weissert_11-2" class="reference"><a href="#cite_note-Leist_and_Weissert-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> </p><p>Cladribine is taken up by specific nucleoside transporter proteins. Once inside a cell, cladribine undergoes phosphorylation by the enzyme deoxycytidine kinase (DCK) to produce mononucleotide 2-chlorodeoxyadenosine 5’monophosphate (2-CdAMP), which is subsequently phosphorylated to the triphosphorylated active compound, 2-chlorodeoxyadenosine 5’triphosphate (2-CdATP).<sup id="cite_ref-Leist_and_Weissert_11-3" class="reference"><a href="#cite_note-Leist_and_Weissert-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Giovannoni_Neurotherapeutics_7-7" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p><p>Activated cladribine is incorporated into the DNA synthesis pathway, where it disrupts DNA repair and synthesis, resulting in an accumulation of DNA strand breaks<sup id="cite_ref-Leist_and_Weissert_11-4" class="reference"><a href="#cite_note-Leist_and_Weissert-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Giovannoni_Neurotherapeutics_7-8" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Johnston_2011_19-0" class="reference"><a href="#cite_note-Johnston_2011-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> This is followed by the activation of transcription factor <a href="/wiki/P53" title="P53">p53</a>, the release of <a href="/wiki/Cytochrome_c" title="Cytochrome c">cytochrome c</a> from mitochondria and eventual programmed cell death (apoptosis).<sup id="cite_ref-Johnston_2011_19-1" class="reference"><a href="#cite_note-Johnston_2011-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> This process occurs over approximately 2 months, with a peak level of cell depletion 4–8 weeks after treatment.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p>Another family of enzymes, the 5'-nucleotidase (5'-NT) family, is also capable of dephosphorylating cladribine, making it inactive. The most important subtypes of this group appear to be cytosolic 5'-NT, c-5NCT1A and c-NT1B, which are cytosolically active and specific for purine analogues.<sup id="cite_ref-ReferenceB_21-0" class="reference"><a href="#cite_note-ReferenceB-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p>Accumulation of cladribine into cells is dependent on the ratio of DCK and 5'-NT. This ratio differs between cell types, with high levels in T and B lymphocytes, making them particularly susceptible to cell death. The cells with the highest ratios are B cells, especially germinal centre and naïve B cells. This helps to explain which B cells are more vulnerable to cladribine-mediated apoptosis. DCK is the rate-limiting enzyme for conversion of the cladribine prodrug into its active triphosphate form, leading to the selective depletion of dividing and non-dividing T and B lymphocytes. In contrast, the DCK:5'-NT ratio is relatively low in other cell types, thus sparing numerous non-hematologic cells.<sup id="cite_ref-Leist_and_Weissert_11-5" class="reference"><a href="#cite_note-Leist_and_Weissert-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Giovannoni_Neurotherapeutics_7-9" class="reference"><a href="#cite_note-Giovannoni_Neurotherapeutics-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-ReferenceB_21-1" class="reference"><a href="#cite_note-ReferenceB-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p>In multiple sclerosis, cladribine's effectiveness may be due to depletion of B cells, in particular memory B cells.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> In the pivotal phase 3 clinical trial of oral cladribine in multiple sclerosis, CLARITY, cladribine selectively depleted 80% of peripheral B cells, compared to only 40–45% of CD4+ T cells and 15‒30% CD8+ T cells.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> More recently, cladribine has been shown to induce long term, selective suppression of certain subtypes of B cells, especially memory B cells.<sup id="cite_ref-ReferenceB_21-2" class="reference"><a href="#cite_note-ReferenceB-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p>Although cladribine is selective for B cells, the long-term suppression of memory B cells, which may contribute to its effect in multiple sclerosis, is not explained by gene or protein expression. Instead, cladribine appears to deplete the entire B cell department, but while naïve B cells rapidly move from lymphoid organs, the memory B cell pool repopulates slowly from the bone marrow. Both hairy cell leukemia and B-cell chronic lymphocytic leukaemia are types of B cell blood cancers. </p> <div class="mw-heading mw-heading2"><h2 id="History_in_hairy_cell_leukemia">History in hairy cell leukemia</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=3" title="Edit section: History in hairy cell leukemia"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/Ernest_Beutler" title="Ernest Beutler">Ernest Beutler</a> and <a href="/wiki/Dennis_A._Carson" title="Dennis A. Carson">Dennis A. Carson</a> had studied <a href="/wiki/Adenosine_deaminase_deficiency" title="Adenosine deaminase deficiency">adenosine deaminase deficiency</a> and recognised that because the lack of adenosine deaminase led to the destruction of B cell lymphocytes, a drug designed to inhibit adenosine deaminase might be useful in lymphomas. Carson then synthesised cladribine, and through clinical research at Scripps starting in the 1980s, Beutler tested it as intravenous infusion and found it was especially useful to treat hairy cell leukemia. No pharmaceutical companies were interested in selling the drug because hairy cell leukemia was an <a href="/wiki/Orphan_disease" class="mw-redirect" title="Orphan disease">orphan disease</a>, so Beutler's lab synthesised and packaged it and supplied it to the hospital pharmacy; the laboratory also developed a test to monitor blood levels. This was the first treatment that led to prolonged remission of hairy cell leukemia, which was previously untreatable.<sup id="cite_ref-NASbeutler_24-0" class="reference"><a href="#cite_note-NASbeutler-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 14–15">: 14–15 </span></sup> </p><p>In February 1991, Scripps began a collaboration with <a href="/wiki/Johnson_%26_Johnson" title="Johnson & Johnson">Johnson & Johnson</a> to bring intravenous cladribine to market, and by December of that year, Johnson & Johnson had filed a <a href="/wiki/New_drug_application" class="mw-redirect" title="New drug application">new drug application</a>; cladribine was approved by the FDA in 1993 for hairy cell leukemia as an <a href="/wiki/Orphan_drug" title="Orphan drug">orphan drug</a>,<sup id="cite_ref-Pink1993_25-0" class="reference"><a href="#cite_note-Pink1993-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> and was approved in Europe later that year.<sup id="cite_ref-EMAsciLitak_26-0" class="reference"><a href="#cite_note-EMAsciLitak-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 2">: 2 </span></sup> </p><p>The subcutaneous formulation was developed in Switzerland in the early 1990s and it was commercialised by Lipomed GmbH in the 2000s.<sup id="cite_ref-EMAsciLitak_26-1" class="reference"><a href="#cite_note-EMAsciLitak-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 2">: 2 </span></sup><sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Safety_profile_of_cladribine_in_hairy_cell_leukemia">Safety profile of cladribine in hairy cell leukemia</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=4" title="Edit section: Safety profile of cladribine in hairy cell leukemia"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Injectable cladribine suppresses the body's ability to make new lymphocytes, <a href="/wiki/Natural_killer_cells" class="mw-redirect" title="Natural killer cells">natural killer cells</a>, and <a href="/wiki/Neutrophils" class="mw-redirect" title="Neutrophils">neutrophils</a> (called <a href="/wiki/Bone_marrow_suppression" title="Bone marrow suppression">myelosuppression</a>); data from hairy cell leukemia studies showed that about 70% of people taking the drug developed <a href="/wiki/Neutropenia" title="Neutropenia">dangerously low levels of white blood cells</a> and about 30% developed infections and some of those progressed to <a href="/wiki/Septic_shock" title="Septic shock">septic shock</a>; about 40% of people taking the drug had fewer <a href="/wiki/Red_blood_cells" class="mw-redirect" title="Red blood cells">red blood cells</a> and became severely <a href="/wiki/Anemia" title="Anemia">anaemic</a>; and about 10% of people had too few <a href="/wiki/Platelets" class="mw-redirect" title="Platelets">platelets</a>.<sup id="cite_ref-Label_14-2" class="reference"><a href="#cite_note-Label-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> At the dosage used to treat hairy cell leukemia in two clinical trials, 16% of people had rashes and 22% had nausea, the nausea generally did not lead to vomiting.<sup id="cite_ref-Label_14-3" class="reference"><a href="#cite_note-Label-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="History_in_multiple_sclerosis">History in multiple sclerosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=5" title="Edit section: History in multiple sclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In the mid-1990s, Beutler, in collaboration with Jack Sipe, a neurologist at Scripps Institute, ran several clinical trials exploring the utility of cladribine in multiple sclerosis, based on the drug's immunosuppressive effects. Sipe's insight into multiple sclerosis, and Beutler's interest in multiple sclerosis due to his sister having the disease, initiated a very productive collaboration.<sup id="cite_ref-Sauter_E_28-0" class="reference"><a href="#cite_note-Sauter_E-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> Ortho-Clinical, a subsidiary of Johnson & Johnson, filed a new drug application for cladribine for multiple sclerosis in 1997 but withdrew it in the late 1990s after discussion with the FDA proved that more clinical data would be needed.<sup id="cite_ref-Sauter_E_28-1" class="reference"><a href="#cite_note-Sauter_E-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p><p>Ivax acquired the rights for oral administration of cladribine to treat multiple sclerosis from Scripps in 2000,<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> and partnered with Serono in 2002.<sup id="cite_ref-WSJSerono_30-0" class="reference"><a href="#cite_note-WSJSerono-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> Ivax was acquired by <a href="/wiki/Teva_Pharmaceutical_Industries" class="mw-redirect" title="Teva Pharmaceutical Industries">Teva</a> in 2006,<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/Merck_KGaA" class="mw-redirect" title="Merck KGaA">Merck KGaA</a> acquired control of Serono's drug business in 2006.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p><p>An oral formulation of the drug with <a href="/wiki/Cyclodextrin" title="Cyclodextrin">cyclodextrin</a> was developed<sup id="cite_ref-MovectroWithdraw_34-0" class="reference"><a href="#cite_note-MovectroWithdraw-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 16">: 16 </span></sup> by Ivax and Serono, and then Merck KGaA conducted clinical trials. Merck KGaA submitted an application to the <a href="/wiki/European_Medicines_Agency" title="European Medicines Agency">European Medicines Agency</a> in 2009, which was rejected in 2010, and an appeal was denied in 2011.<sup id="cite_ref-MovectroWithdraw_34-1" class="reference"><a href="#cite_note-MovectroWithdraw-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 4–5">: 4–5 </span></sup> Likewise Merck KGaA's new drug application with the FDA rejected in 2011.<sup id="cite_ref-MedPage_35-0" class="reference"><a href="#cite_note-MedPage-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p><p>The ratio of benefit to harm was not clear to regulators, and further studies were requested to address concerns related to severe lymphopenia and cancer cases observed during pivotal trials.<sup id="cite_ref-MovectroWithdraw_34-2" class="reference"><a href="#cite_note-MovectroWithdraw-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 54–55">: 54–55 </span></sup> Clinical studies of multiple sclerosis were still ongoing at the time of the rejections, and Merck KGaA committed to completing them.<sup id="cite_ref-MedPage_35-1" class="reference"><a href="#cite_note-MedPage-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> A meta-analysis of data from clinical trials comparing the risk of cancer and other disease-modifying therapies showed that cladribine tablets did not increase the risk of cancer at the doses used in the initial clinical trials.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p><p>Based on the supporting data from the completed clinical trials that confirmed no increased risk of cancer, Merck announced it would again seek regulatory approval.<sup id="cite_ref-37" class="reference"><a href="#cite_note-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> In 2016, the EMA accepted its application for review.<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> On 22 June 2017, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the treatment of relapsing forms of multiple sclerosis.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> </p><p>Cladribine tablets were later approved in Europe, in August 2017, for highly active relapsing-remitting multiple sclerosis, and has since been approved by the FDA for the treatment of relapsing-remitting and secondary progressive multiple sclerosis in the US.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Use_in_multiple_sclerosis">Use in multiple sclerosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=6" title="Edit section: Use in multiple sclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>As per the EU label, cladribine tablets are indicated for the treatment of adult patients with highly active relapsing multiple sclerosis as defined by clinical or imaging features: (i) patients with a relapse in the previous year and at least one T1 Gd+ lesion or 9 or more T2 lesions, while on another disease-modifying therapies or (ii) patients with two or more relapses in the previous year, whether on disease-modifying treatment or not.<sup id="cite_ref-EMA_2021_10-1" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>Two main approaches to multiple sclerosis treatment maintenance therapy are used – immunomodulation and <a href="/wiki/Immunosuppression" title="Immunosuppression">immunosuppression</a> and alternatively, immune reconstitution therapy. Classified as the latter, cladribine tablets are administered intermittently as a short treatment course without continuous immunosuppression. In contrast to maintenance therapies, clinical efficacy extends beyond the dosing period.<sup id="cite_ref-pmid30944586_41-0" class="reference"><a href="#cite_note-pmid30944586-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid29634596_42-0" class="reference"><a href="#cite_note-pmid29634596-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid28626781_43-0" class="reference"><a href="#cite_note-pmid28626781-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </p><p>Cladribine tablets are administered as 2 courses separated by 1 year (a maximum of 20 days of treatment). The recommended cumulative dose is 3.5 mg/kg weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (1 or 2 tablets) as a single daily dose based on body weight.<sup id="cite_ref-EMA_2021_10-2" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>Before initiating treatment with cladribine tablets, blood tests, MRI and infection screening must be performed. Due to an increased risk of <a href="/wiki/Shingles" title="Shingles">herpes zoster</a> with cladribine tablets, patients who are antibody-negative for varicella zoster virus are recommended to be vaccinated before starting treatment. Treatment should not be initiated within 4 to 6 weeks of receiving a live or attenuated live vaccine because of a risk of active infection. Vaccination with live or attenuated live vaccines should also be avoided during and after treatment, but can be considered when lymphocyte counts have recovered to ≥1000 cells/mm<sup>3</sup>.<sup id="cite_ref-EMA_2021_10-3" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>Following completion of the two treatment courses, no further treatment or additional monitoring is required.<sup id="cite_ref-EMA_2021_10-4" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>The use of cladribine tablets is contraindicated in pregnant women, and women of childbearing potential must use effective contraception to prevent pregnancy during treatment and 6 months after receiving the last dose.<sup id="cite_ref-EMA_2021_10-5" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Efficacy_of_cladribine_tablets_in_multiple_sclerosis">Efficacy of cladribine tablets in multiple sclerosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=7" title="Edit section: Efficacy of cladribine tablets in multiple sclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Clinical trial results have shown that cladribine tablets can be an effective treatment for highly active, relapsing forms of multiple sclerosis, with significant clinical benefits in relapse rate, disability progression, and radiological measures.<sup id="cite_ref-Giovannoni_Mult_Scler_2018_44-0" class="reference"><a href="#cite_note-Giovannoni_Mult_Scler_2018-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> Compared with placebo, patients who received cladribine tablets (3.5 mg/kg) in the CLARITY study had a 58% reduction in annualized relapse rate<sup id="cite_ref-Giovannoni_N_Engl_J_Med_2010_45-0" class="reference"><a href="#cite_note-Giovannoni_N_Engl_J_Med_2010-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> and 47% of patients showed no evidence of disease activity at 2 years.<sup id="cite_ref-Giovannoni_Lancet_2011_46-0" class="reference"><a href="#cite_note-Giovannoni_Lancet_2011-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> Clinical improvements can be observed at Week 24 of treatment,<sup id="cite_ref-Giovannoni_Lancet_2011_46-1" class="reference"><a href="#cite_note-Giovannoni_Lancet_2011-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Comi_2013_47-0" class="reference"><a href="#cite_note-Comi_2013-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Schippling_ECTRIMS_2018_48-0" class="reference"><a href="#cite_note-Schippling_ECTRIMS_2018-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> and benefits may be sustained up to 4 years, beyond the 2-year dosing period and recovery of total lymphocytes.<sup id="cite_ref-Giovannoni_Mult_Scler_2018_44-1" class="reference"><a href="#cite_note-Giovannoni_Mult_Scler_2018-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Comi_2019_49-0" class="reference"><a href="#cite_note-Comi_2019-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Gavin_EAN_2017_50-0" class="reference"><a href="#cite_note-Gavin_EAN_2017-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> <i>Post-hoc</i> analyses of clinical trial data showed that 89% of patients remained free from disability progression two years after treatment.<sup id="cite_ref-51" class="reference"><a href="#cite_note-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> </p><p>Further analyses of a subgroup of patients in the CLARITY study who had very active multiple sclerosis showed a 67% reduction in relapse rates and an 82% reduction in disability progression in those treated with cladribine tablets. Similarly, clinical improvements were seen in lesion burden on MRI scans in this population.<sup id="cite_ref-Giovannoni_Mult_Scler_2019_52-0" class="reference"><a href="#cite_note-Giovannoni_Mult_Scler_2019-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> </p><p>Studies evaluating the treatment effects of cladribine tablets across a spectrum of baseline demographics and disease characteristics showed that the relative risk of relapse was significantly reduced compared with placebo, irrespective of previous treatment experience.<sup id="cite_ref-53" class="reference"><a href="#cite_note-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup> </p><p>Furthermore, treatment with cladribine tablets has been shown to significantly reduce the rate of brain atrophy in patients with highly active relapsing-remitting multiple sclerosis. This reduction correlated with a reduced risk in disability progression in a retrospective analysis.<sup id="cite_ref-pmid28140753_54-0" class="reference"><a href="#cite_note-pmid28140753-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> </p><p>In clinical trials, higher cumulative doses of cladribine tablets did not result in further improvement in efficacy nor did additional courses after the 2-year treatment period, but was associated with a higher incidence of Grade 3 and Grade 4 lymphopenia.<sup id="cite_ref-EMA_2021_10-6" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Giovannoni_Mult_Scler_2018_44-2" class="reference"><a href="#cite_note-Giovannoni_Mult_Scler_2018-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Safety_profile_of_cladribine_tablets_in_multiple_sclerosis">Safety profile of cladribine tablets in multiple sclerosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=8" title="Edit section: Safety profile of cladribine tablets in multiple sclerosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Cladribine tablets target the cells of the <a href="/wiki/Adaptive_immune_system" title="Adaptive immune system">adaptive immune system</a> with minimal impact on innate immune cells. Although the exact mechanism by which cladribine exerts its therapeutic effect is not fully elucidated, it is proposed to have a transient effect on B and T lymphocyte depletion, interrupting the cascade of immune events central to multiple sclerosis. As a result, a reduction in lymphocyte count (<a href="/wiki/Lymphocytopenia" title="Lymphocytopenia">lymphopenia</a>) may be reported following treatment.<sup id="cite_ref-EMA_2021_10-7" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> In clinical trials, lymphocyte levels above Grade 0 (≥1000 cells/mm<sup>3</sup>) and Grade 1 (<1000–800 cells/mm<sup>3</sup>) were maintained in most patients, with levels continuing to improve after the 2-year dosing period.<sup id="cite_ref-Comi_2019_49-1" class="reference"><a href="#cite_note-Comi_2019-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> Less than 1% of patients developed Grade 4 lymphopenia (<200 cells/mm<sup>3</sup>). It is important that patients with lymphocyte counts below 500 cells/mm<sup>3</sup> should be actively monitored for signs suggestive of infection and that anti-infective treatments are given to at-risk patients.<sup id="cite_ref-EMA_2021_10-8" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Cook_2019_55-0" class="reference"><a href="#cite_note-Cook_2019-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> </p><p>Despite the initial reduction in lymphocyte counts following treatment, studies showed the overall risk of infection in patients receiving cladribine tablets was comparable to those who received placebo, except for herpes zoster infection.<sup id="cite_ref-Cook_2019_55-1" class="reference"><a href="#cite_note-Cook_2019-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> Due to this increased risk, it is recommended that patients are screened for varicella zoster virus and antibody-negative patients are vaccinated prior to receiving treatment.<sup id="cite_ref-EMA_2021_10-9" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> In an analysis of post-approval data, as of 2020, no new infection safety signals were observed in over 18,000 patients.<sup id="cite_ref-Giovannoni_ACTRIMS-ECTRIMS_2020_56-0" class="reference"><a href="#cite_note-Giovannoni_ACTRIMS-ECTRIMS_2020-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Progressive_multifocal_leukoencephalopathy" title="Progressive multifocal leukoencephalopathy">Progressive multifocal leukoencephalopathy</a> has been reported in patients with hairy cell leukemia treated with parenteral cladribine.<sup id="cite_ref-EMA_2021_10-10" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> However, in up to 10 years of follow-up of patients receiving cladribine tablets for multiple sclerosis, no cases of progressive multifocal leukoencephalopathy have been observed; baseline MRI must be performed prior to initiating treatment.<sup id="cite_ref-EMA_2021_10-11" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>In clinical trials, malignancies were observed more frequently in patients treated with cladribine tablets compared with patients who received placebo. Compared with a matched reference population from the Global Cancer Observatory database, cladribine tablets had no increased risk of <a href="/wiki/Malignancy" title="Malignancy">malignancy</a> in long-term real-world evidence data.<sup id="cite_ref-EMA_2021_10-12" class="reference"><a href="#cite_note-EMA_2021-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Cook_2019_55-2" class="reference"><a href="#cite_note-Cook_2019-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Research">Research</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=9" title="Edit section: Research"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Cladribine has been studied as part of a multidrug <a href="/wiki/Chemotherapy_regimen" title="Chemotherapy regimen">chemotherapy regimen</a> for drug-resistant <a href="/wiki/T-cell_prolymphocytic_leukemia" title="T-cell prolymphocytic leukemia">T-cell prolymphocytic leukaemia</a>.<sup id="cite_ref-57" class="reference"><a href="#cite_note-57"><span class="cite-bracket">[</span>57<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Cladribine&action=edit&section=10" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-drugs.comINT-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-drugs.comINT_1-0">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation 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(June 2015). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807901">"Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia"</a>. <i>Science Translational Medicine</i>. <b>7</b> (293): 293ra102. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1126%2Fscitranslmed.aaa5079">10.1126/scitranslmed.aaa5079</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807901">4807901</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/26109102">26109102</a>.</cite><span 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class="nowraplinks hlist mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini 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href="/wiki/Special:EditPage/Template:Demyelinating_diseases_of_CNS" title="Special:EditPage/Template:Demyelinating diseases of CNS"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Demyelinating_diseases_of_the_central_nervous_system208" style="font-size:114%;margin:0 4em">Demyelinating diseases of the <a href="/wiki/Central_nervous_system" title="Central nervous system">central nervous system</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Signs_and_symptoms_of_multiple_sclerosis" title="Signs and symptoms of multiple sclerosis">Signs and symptoms</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ataxia" title="Ataxia">Ataxia</a></li> <li><a href="/wiki/Major_depressive_disorder" title="Major depressive disorder">Depression</a></li> <li><a href="/wiki/Diplopia" title="Diplopia">Diplopia</a></li> <li><a href="/wiki/Dysarthria" title="Dysarthria">Dysarthria</a></li> <li><a href="/wiki/Dysphagia" title="Dysphagia">Dysphagia</a></li> <li><a href="/wiki/Fatigue" title="Fatigue">Fatigue</a></li> <li><a href="/wiki/Urinary_incontinence" title="Urinary incontinence">Incontinence</a></li> <li><a href="/wiki/Nystagmus" title="Nystagmus">Nystagmus</a></li> <li><a href="/wiki/Optic_neuritis" title="Optic neuritis">Optic neuritis</a></li> <li><a href="/wiki/Pain" title="Pain">Pain</a></li> <li><a href="/wiki/Uhthoff%27s_phenomenon" title="Uhthoff's phenomenon">Uhthoff's phenomenon</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Investigations and diagnosis</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Diagnosis_of_multiple_sclerosis" title="Diagnosis of multiple sclerosis">Diagnosis of multiple sclerosis</a> <ul><li><a href="/wiki/McDonald_criteria" title="McDonald criteria">McDonald criteria</a></li></ul></li> <li><a href="/wiki/Poser_criteria" title="Poser criteria">Poser criteria</a></li></ul> <ul><li>Clinical <ul><li><a href="/wiki/Clinically_isolated_syndrome" title="Clinically isolated syndrome">Clinically isolated syndrome</a></li> <li><a href="/wiki/Expanded_Disability_Status_Scale" title="Expanded Disability Status Scale">Expanded Disability Status Scale</a></li></ul></li> <li>Serological and CSF <ul><li><a href="/wiki/Oligoclonal_band" title="Oligoclonal band">Oligoclonal bands</a></li></ul></li> <li>Radiological <ul><li><a href="/wiki/Radiologically_isolated_syndrome" title="Radiologically isolated syndrome">Radiologically isolated syndrome</a></li> <li><a href="/wiki/Lesional_demyelinations_of_the_central_nervous_system" title="Lesional demyelinations of the central nervous system">Lesional demyelinations of the central nervous system</a></li> <li><a href="/wiki/Dawson%27s_fingers" class="mw-redirect" title="Dawson's fingers">Dawson's fingers</a></li></ul></li> <li><a href="/wiki/Frexalimab" title="Frexalimab">Frexalimab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Approved treatment</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Management_of_multiple_sclerosis" title="Management of multiple sclerosis">Management of multiple sclerosis</a></li> <li><a href="/wiki/Alemtuzumab" title="Alemtuzumab">Alemtuzumab</a></li> <li><a class="mw-selflink selflink">Cladribine</a></li> <li><a href="/wiki/Dimethyl_fumarate" title="Dimethyl fumarate">Dimethyl fumarate</a></li> <li><a href="/wiki/Diroximel_fumarate" title="Diroximel fumarate">Diroximel fumarate</a></li> <li><a href="/wiki/Fingolimod" title="Fingolimod">Fingolimod</a></li> <li><a href="/wiki/Glatiramer_acetate" title="Glatiramer acetate">Glatiramer acetate</a></li> <li><a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">Interferon beta-1a</a></li> <li><a href="/wiki/Interferon_beta-1b" title="Interferon beta-1b">Interferon beta-1b</a></li> <li><a href="/wiki/Laquinimod" title="Laquinimod">Laquinimod</a></li> <li><a href="/wiki/Mitoxantrone" title="Mitoxantrone">Mitoxantrone</a></li> <li><a href="/wiki/Monomethyl_fumarate" title="Monomethyl fumarate">Monomethyl fumarate</a></li> <li><a href="/wiki/Natalizumab" title="Natalizumab">Natalizumab</a></li> <li><a href="/wiki/Ocrelizumab" title="Ocrelizumab">Ocrelizumab</a> (<a href="/wiki/Ocrelizumab/hyaluronidase" title="Ocrelizumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Ozanimod" title="Ozanimod">Ozanimod</a></li> <li><a href="/wiki/Ponesimod" title="Ponesimod">Ponesimod</a></li> <li><a href="/wiki/Siponimod" title="Siponimod">Siponimod</a></li> <li><a href="/wiki/Teriflunomide" title="Teriflunomide">Teriflunomide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other treatments</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Former <ul><li><a href="/wiki/Daclizumab" title="Daclizumab">Daclizumab</a></li></ul></li> <li><a href="/wiki/Research_in_multiple_sclerosis" title="Research in multiple sclerosis">Research in multiple sclerosis</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Demyelinating diseases</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/CNS_demyelinating_autoimmune_diseases" title="CNS demyelinating autoimmune diseases">Autoimmune</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Neuromyelitis_optica_spectrum_disorder" title="Neuromyelitis optica spectrum disorder">Neuromyelitis optica spectrum disorder</a></li> <li><a href="/wiki/Diffuse_myelinoclastic_sclerosis" title="Diffuse myelinoclastic sclerosis">Diffuse myelinoclastic sclerosis</a></li> <li><a href="/wiki/MOG_antibody_disease" title="MOG antibody disease">MOG antibody disease</a></li> <li><a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">Multiple sclerosis</a></li> <li><a href="/wiki/Chronic_inflammatory_demyelinating_polyneuropathy" title="Chronic inflammatory demyelinating polyneuropathy">Chronic inflammatory demyelinating polyneuropathy</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Inflammatory_demyelinating_diseases_of_the_central_nervous_system" title="Inflammatory demyelinating diseases of the central nervous system">Inflammatory</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Acute_disseminated_encephalomyelitis" title="Acute disseminated encephalomyelitis">Acute disseminated encephalomyelitis</a></li> <li><a href="/wiki/Balo_concentric_sclerosis" title="Balo concentric sclerosis">Balo concentric sclerosis</a></li> <li><a href="/wiki/Marburg_acute_multiple_sclerosis" title="Marburg acute multiple sclerosis">Marburg acute multiple sclerosis</a></li> <li><a href="/wiki/Neuromyelitis_optica_spectrum_disorder" title="Neuromyelitis optica spectrum disorder">Neuromyelitis optica spectrum disorder</a></li> <li><a href="/wiki/Diffuse_myelinoclastic_sclerosis" title="Diffuse myelinoclastic sclerosis">Diffuse myelinoclastic sclerosis</a></li> <li><a href="/wiki/Tumefactive_multiple_sclerosis" title="Tumefactive multiple sclerosis">Tumefactive multiple sclerosis</a></li> <li><a href="/wiki/Experimental_autoimmune_encephalomyelitis" title="Experimental autoimmune encephalomyelitis">Experimental autoimmune encephalomyelitis</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Hereditary_CNS_demyelinating_disease" title="Hereditary CNS demyelinating disease">Hereditary</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adrenoleukodystrophy" title="Adrenoleukodystrophy">Adrenoleukodystrophy</a></li> <li><a href="/wiki/Alexander_disease" title="Alexander disease">Alexander disease</a></li> <li><a href="/wiki/Canavan_disease" title="Canavan disease">Canavan disease</a></li> <li><a href="/wiki/Krabbe_disease" title="Krabbe disease">Krabbe disease</a></li> <li><a href="/wiki/Metachromatic_leukodystrophy" title="Metachromatic leukodystrophy">Metachromatic leukodystrophy</a></li> <li><a href="/wiki/Pelizaeus%E2%80%93Merzbacher_disease" title="Pelizaeus–Merzbacher disease">Pelizaeus–Merzbacher disease</a></li> <li><a href="/wiki/Leukoencephalopathy_with_vanishing_white_matter" title="Leukoencephalopathy with vanishing white matter">Leukoencephalopathy with vanishing white matter</a></li> <li><a href="/wiki/Megalencephalic_leukoencephalopathy_with_subcortical_cysts" title="Megalencephalic leukoencephalopathy with subcortical cysts">Megalencephalic leukoencephalopathy with subcortical cysts</a></li> <li><a href="/wiki/CAMFAK_syndrome" title="CAMFAK syndrome">CAMFAK syndrome</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Central_pontine_myelinolysis" title="Central pontine myelinolysis">Central pontine myelinolysis</a></li> <li><a href="/wiki/Marchiafava%E2%80%93Bignami_disease" title="Marchiafava–Bignami disease">Marchiafava–Bignami disease</a></li> <li><a href="/wiki/Mitochondrial_DNA_depletion_syndrome" title="Mitochondrial DNA depletion syndrome">Mitochondrial DNA depletion syndrome</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/List_of_multiple_sclerosis_organizations" title="List of multiple sclerosis organizations">List of multiple sclerosis organizations</a></li> <li><a href="/wiki/List_of_people_with_multiple_sclerosis" title="List of people with multiple sclerosis">List of people with multiple sclerosis</a></li> <li><a href="/wiki/Multiple_sclerosis_drug_pipeline" title="Multiple sclerosis drug pipeline">Multiple sclerosis drug pipeline</a></li> <li><a href="/wiki/Pathophysiology_of_multiple_sclerosis" title="Pathophysiology of multiple sclerosis">Pathophysiology</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Merck_Serono31" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Merck_Serono" title="Template:Merck Serono"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Merck_Serono" title="Template talk:Merck Serono"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Merck_Serono" title="Special:EditPage/Template:Merck Serono"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Merck_Serono31" style="font-size:114%;margin:0 4em"><a href="/wiki/Merck_Serono" title="Merck Serono">Merck Serono</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Products</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Avelumab" title="Avelumab">Avelumab</a></li> <li><a href="/wiki/Bisoprolol" title="Bisoprolol">Bisoprolol</a></li> <li><a href="/wiki/Cetuximab" title="Cetuximab">Cetuximab</a></li> <li><a class="mw-selflink selflink">Cladribine</a></li> <li><a href="/wiki/Efalizumab" title="Efalizumab">Efalizumab</a></li> <li><a href="/wiki/Gonadotropin_preparations" title="Gonadotropin preparations">Gonadotropin preparations</a></li> <li><a href="/wiki/Human_chorionic_gonadotropin" title="Human chorionic gonadotropin">Human chorionic gonadotropin</a></li> <li><a href="/wiki/Interferon_beta-1a" title="Interferon beta-1a">Interferon beta-1a</a></li> <li><a href="/wiki/Levothyroxine" title="Levothyroxine">Levothyroxine</a></li> <li><a href="/wiki/Luteinizing_hormone" title="Luteinizing hormone">Luteinizing hormone</a></li> <li><a href="/wiki/Metformin" title="Metformin">Metformin</a></li> <li><a href="/wiki/Mitoxantrone" title="Mitoxantrone">Mitoxantrone</a></li> <li><a href="/wiki/Saizen" title="Saizen">Saizen</a></li> <li><a href="/wiki/Serostim" title="Serostim">Serostim</a></li> <li><a href="/wiki/Tegafur/uracil" title="Tegafur/uracil">Tegafur/uracil</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Related</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Merck_Group" title="Merck Group">Merck Group</a></li> <li><a href="/wiki/Serono" title="Serono">Serono</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"></div><div role="navigation" class="navbox" aria-labelledby="Intracellular_chemotherapeutic_agents_/_antineoplastic_agents_(L01)604" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Chemotherapeutic_agents" title="Template:Chemotherapeutic agents"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Chemotherapeutic_agents" class="mw-redirect" title="Template talk:Chemotherapeutic agents"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Chemotherapeutic_agents" title="Special:EditPage/Template:Chemotherapeutic agents"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Intracellular_chemotherapeutic_agents_/_antineoplastic_agents_(L01)604" style="font-size:114%;margin:0 4em">Intracellular <a href="/wiki/Chemotherapy" title="Chemotherapy">chemotherapeutic agents</a> / <a href="/wiki/Antineoplastic" class="mw-redirect" title="Antineoplastic">antineoplastic agents</a> (<a href="/wiki/ATC_code_L01" title="ATC code L01">L01</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Spindle_poison" title="Spindle poison">SPs</a>/<a href="/wiki/Mitotic_inhibitor" title="Mitotic inhibitor">MIs</a><br />(<a href="/wiki/M_phase" class="mw-redirect" title="M phase">M phase</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Block <a href="/wiki/Microtubule" title="Microtubule">microtubule</a> assembly</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Vinca_alkaloid" title="Vinca alkaloid">Vinca alkaloids</a></i> (<a href="/wiki/Vinblastine" title="Vinblastine">Vinblastine</a><sup>#</sup></li> <li><a href="/wiki/Vincristine" title="Vincristine">Vincristine</a><sup>#</sup></li> <li><a href="/wiki/Vindesine" title="Vindesine">Vindesine</a></li> <li><a href="/wiki/Vinflunine" title="Vinflunine">Vinflunine</a><sup>§</sup></li> <li><a href="/wiki/Vinorelbine" title="Vinorelbine">Vinorelbine</a><sup>#</sup>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Block microtubule disassembly</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Taxane" title="Taxane">Taxanes</a></i> (<a href="/wiki/Cabazitaxel" title="Cabazitaxel">Cabazitaxel</a></li> <li><a href="/wiki/Docetaxel" title="Docetaxel">Docetaxel</a><sup>#</sup></li> <li><a href="/wiki/Larotaxel" title="Larotaxel">Larotaxel</a></li> <li><a href="/wiki/Ortataxel" title="Ortataxel">Ortataxel</a><sup>†</sup></li> <li><a href="/wiki/Paclitaxel" title="Paclitaxel">Paclitaxel</a><sup>#</sup></li> <li><a href="/wiki/Tesetaxel" title="Tesetaxel">Tesetaxel</a>)</li> <li><i><a href="/wiki/Epothilone" title="Epothilone">Epothilones</a></i> (<a href="/wiki/Ixabepilone" title="Ixabepilone">Ixabepilone</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/DNA_replication" title="DNA replication">DNA replication</a><br />inhibitor</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">DNA precursors/<br /><a href="/wiki/Antimetabolite" title="Antimetabolite">antimetabolites</a><br />(<a href="/wiki/S_phase" title="S phase">S phase</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Antifolate" title="Antifolate">Folic acid</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Dihydrofolate_reductase_inhibitor" title="Dihydrofolate reductase inhibitor">Dihydrofolate reductase inhibitor</a></i> (<a href="/wiki/Aminopterin" title="Aminopterin">Aminopterin</a></li> <li><a href="/wiki/Methotrexate" title="Methotrexate">Methotrexate</a><sup>#</sup></li> <li><a href="/wiki/Pemetrexed" title="Pemetrexed">Pemetrexed</a></li> <li><a href="/wiki/Pralatrexate" title="Pralatrexate">Pralatrexate</a>)</li> <li><i><a href="/wiki/Thymidylate_synthase_inhibitor" title="Thymidylate synthase inhibitor">Thymidylate synthase inhibitor</a></i> (<a href="/wiki/Pemetrexed" title="Pemetrexed">Pemetrexed</a></li> <li><a href="/wiki/Raltitrexed" title="Raltitrexed">Raltitrexed</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Purine_analogue" title="Purine analogue">Purine</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Adenosine_deaminase_inhibitor" class="mw-redirect" title="Adenosine deaminase inhibitor">Adenosine deaminase inhibitor</a></i> (<a href="/wiki/Pentostatin" title="Pentostatin">Pentostatin</a>)</li></ul> <ul><li><i><a href="/wiki/Halogenation" title="Halogenation">Halogenated</a>/<a href="/wiki/Ribonucleotide_reductase_inhibitor" title="Ribonucleotide reductase inhibitor">ribonucleotide reductase inhibitors</a></i> (<a class="mw-selflink selflink">Cladribine</a></li> <li><a href="/wiki/Clofarabine" title="Clofarabine">Clofarabine</a></li> <li><a href="/wiki/Fludarabine" title="Fludarabine">Fludarabine</a>)</li> <li><a href="/wiki/Nelarabine" title="Nelarabine">Nelarabine</a></li> <li><a href="/wiki/Rabacfosadine" title="Rabacfosadine">Rabacfosadine</a></li> <li><i><a href="/wiki/Thiopurine" title="Thiopurine">Thiopurine</a></i> (<a href="/wiki/Mercaptopurine" title="Mercaptopurine">Mercaptopurine</a><sup>#</sup></li> <li><a href="/wiki/Tioguanine" title="Tioguanine">Tioguanine</a><sup>#</sup>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Pyrimidine_analogue" title="Pyrimidine analogue">Pyrimidine</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Thymidylate_synthase_inhibitor" title="Thymidylate synthase inhibitor">Thymidylate synthase inhibitor</a></i> (<a href="/wiki/Capecitabine" title="Capecitabine">Capecitabine</a><sup>#</sup></li> <li><a href="/wiki/Carmofur" title="Carmofur">Carmofur</a></li> <li><a href="/wiki/Doxifluridine" title="Doxifluridine">Doxifluridine</a></li> <li><a href="/wiki/Floxuridine" title="Floxuridine">Floxuridine</a></li> <li><a href="/wiki/Fluorouracil" title="Fluorouracil">Fluorouracil</a><sup>#</sup></li> <li><a href="/wiki/Tegafur" title="Tegafur">Tegafur</a> (<a href="/wiki/Tegafur/gimeracil/oteracil" title="Tegafur/gimeracil/oteracil">+gimeracil/oteracil</a>))</li></ul> <ul><li><i><a href="/wiki/DNA_polymerase_inhibitor" class="mw-redirect" title="DNA polymerase inhibitor">DNA polymerase inhibitor</a></i> (<a href="/wiki/Cytarabine" title="Cytarabine">Cytarabine</a><sup>#</sup> <a href="/wiki/Daunorubicin/cytarabine" title="Daunorubicin/cytarabine">+daunorubicin</a>)</li></ul> <ul><li><i><a href="/wiki/Ribonucleotide_reductase_inhibitor" title="Ribonucleotide reductase inhibitor">Ribonucleotide reductase inhibitor</a></i> (<a href="/wiki/Gemcitabine" title="Gemcitabine">Gemcitabine</a><sup>#</sup>)</li></ul> <ul><li><i><a href="/wiki/Hypomethylating_agent" title="Hypomethylating agent">Hypomethylating agent</a></i> (<a href="/wiki/Azacitidine" title="Azacitidine">Azacitidine</a></li> <li><a href="/wiki/Decitabine" title="Decitabine">Decitabine</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Deoxyribonucleotide" title="Deoxyribonucleotide">Deoxyribonucleotide</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Ribonucleotide_reductase_inhibitor" title="Ribonucleotide reductase inhibitor">Ribonucleotide reductase inhibitor</a></i> (<a href="/wiki/Hydroxycarbamide" title="Hydroxycarbamide">Hydroxycarbamide</a><sup>#</sup>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Topoisomerase_inhibitor" title="Topoisomerase inhibitor">Topoisomerase inhibitors</a><br />(<a href="/wiki/S_phase" title="S phase">S phase</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_I_topoisomerase#Inhibition" title="Type I topoisomerase">I</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Camptotheca" title="Camptotheca">Camptotheca</a></i> (<a href="/wiki/Belotecan" title="Belotecan">Belotecan</a></li> <li><a href="/wiki/Camptothecin" title="Camptothecin">Camptothecin</a></li> <li><a href="/w/index.php?title=Cositecan&action=edit&redlink=1" class="new" title="Cositecan (page does not exist)">Cositecan</a><sup>†</sup></li> <li><a href="/wiki/Etirinotecan_pegol" title="Etirinotecan pegol">Etirinotecan pegol</a><sup>†</sup></li> <li><a href="/wiki/Exatecan" title="Exatecan">Exatecan</a></li> <li><a href="/w/index.php?title=Gimatecan&action=edit&redlink=1" class="new" title="Gimatecan (page does not exist)">Gimatecan</a></li> <li><a href="/wiki/Irinotecan" title="Irinotecan">Irinotecan</a><sup>#</sup></li> <li><a href="/wiki/Lurtotecan" title="Lurtotecan">Lurtotecan</a><sup>‡</sup></li> <li><a href="/wiki/Rubitecan" title="Rubitecan">Rubitecan</a><sup>‡</sup></li> <li><a href="/w/index.php?title=Silatecan&action=edit&redlink=1" class="new" title="Silatecan (page does not exist)">Silatecan</a><sup>§</sup></li> <li><a href="/wiki/Topotecan" title="Topotecan">Topotecan</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_II_topoisomerase#Inhibition" title="Type II topoisomerase">II</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Podophyllum_peltatum" title="Podophyllum peltatum">Podophyllum</a></i> (<a href="/wiki/Etoposide" title="Etoposide">Etoposide</a><sup>#</sup></li> <li><a href="/wiki/Teniposide" title="Teniposide">Teniposide</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Type_II_topoisomerase#Inhibition" title="Type II topoisomerase">II</a>+<a href="/wiki/Intercalation_(biochemistry)" title="Intercalation (biochemistry)">Intercalation</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Anthracycline" title="Anthracycline">Anthracyclines</a></i> (<a href="/wiki/Aclarubicin" title="Aclarubicin">Aclarubicin</a></li> <li><a href="/wiki/Amrubicin" title="Amrubicin">Amrubicin</a><sup>†</sup></li> <li><a href="/wiki/Daunorubicin" title="Daunorubicin">Daunorubicin</a><sup>#</sup> (<a href="/wiki/Daunorubicin/cytarabine" title="Daunorubicin/cytarabine">+cytarabine</a>)</li> <li><a href="/wiki/Doxorubicin" title="Doxorubicin">Doxorubicin</a><sup>#</sup></li> <li><a href="/wiki/Epirubicin" title="Epirubicin">Epirubicin</a></li> <li><a href="/wiki/Idarubicin" title="Idarubicin">Idarubicin</a></li> <li><a href="/wiki/Pirarubicin" title="Pirarubicin">Pirarubicin</a></li> <li><a href="/wiki/Valrubicin" title="Valrubicin">Valrubicin</a></li> <li><a href="/wiki/Zorubicin" title="Zorubicin">Zorubicin</a>)</li> <li><i><a href="/wiki/Anthraquinone" title="Anthraquinone">Anthracenediones</a></i> (<a href="/wiki/Losoxantrone" title="Losoxantrone">Losoxantrone</a></li> <li><a href="/wiki/Mitoxantrone" title="Mitoxantrone">Mitoxantrone</a></li> <li><a href="/wiki/Pixantrone" title="Pixantrone">Pixantrone</a>)</li> <li><a href="/wiki/Amsacrine" title="Amsacrine">Amsacrine</a></li> <li><a href="/wiki/Bisantrene" title="Bisantrene">Bisantrene</a></li> <li><a href="/wiki/Crisnatol" title="Crisnatol">Crisnatol</a></li> <li><a href="/wiki/Menogaril" title="Menogaril">Menogaril</a><sup>§</sup></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Crosslinking_of_DNA" title="Crosslinking of DNA">Crosslinking of DNA</a><br />(<a href="/wiki/Cell-cycle_nonspecific_antineoplastic_agents" title="Cell-cycle nonspecific antineoplastic agents">CCNS</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Alkylating_antineoplastic_agent" title="Alkylating antineoplastic agent">Alkylating</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Nitrogen_mustard" title="Nitrogen mustard">Nitrogen mustards</a>:</i> <a href="/wiki/Bendamustine" title="Bendamustine">Bendamustine</a><sup>#</sup></li> <li><a href="/wiki/Chlormethine" title="Chlormethine">Chlormethine</a></li> <li><a href="/wiki/Cyclophosphamide" title="Cyclophosphamide">Cyclophosphamide</a><sup>#</sup> (<a href="/wiki/Ifosfamide" title="Ifosfamide">Ifosfamide</a><sup>#</sup></li> <li><a href="/wiki/Trofosfamide" title="Trofosfamide">Trofosfamide</a>)</li> <li><a href="/wiki/Chlorambucil" title="Chlorambucil">Chlorambucil</a><sup>#</sup></li> <li><a href="/wiki/Melphalan" title="Melphalan">Melphalan</a> (<a href="/wiki/Melphalan_flufenamide" title="Melphalan flufenamide">Melphalan flufenamide</a>)</li> <li><a href="/wiki/Prednimustine" title="Prednimustine">Prednimustine</a></li> <li><a href="/wiki/Uramustine" title="Uramustine">Uramustine</a></li></ul> <ul><li><i><a href="/wiki/Nitrosourea" title="Nitrosourea">Nitrosoureas</a>:</i> <a href="/wiki/Carmustine" title="Carmustine">Carmustine</a></li> <li><a href="/wiki/Fotemustine" title="Fotemustine">Fotemustine</a></li> <li><a href="/wiki/Lomustine" title="Lomustine">Lomustine</a> (<a href="/wiki/Semustine" title="Semustine">Semustine</a>)</li> <li><a href="/wiki/Nimustine" title="Nimustine">Nimustine</a></li> <li><a href="/wiki/Ranimustine" title="Ranimustine">Ranimustine</a></li> <li><a href="/wiki/Streptozotocin" title="Streptozotocin">Streptozocin</a></li></ul> <ul><li><i><a href="/wiki/Alkyl_sulfonate" title="Alkyl sulfonate">Alkyl sulfonates</a>:</i> <a href="/wiki/Busulfan" title="Busulfan">Busulfan</a> (<a href="/wiki/Mannosulfan" title="Mannosulfan">Mannosulfan</a></li> <li><a href="/wiki/Treosulfan" title="Treosulfan">Treosulfan</a>)</li></ul> <ul><li><i><a href="/wiki/Aziridine" title="Aziridine">Aziridines</a>:</i> <a href="/wiki/Carboquone" title="Carboquone">Carboquone</a></li> <li><a href="/wiki/Thiotepa" title="Thiotepa">Thiotepa</a></li> <li><a href="/wiki/Triaziquone" title="Triaziquone">Triaziquone</a></li> <li><a href="/wiki/Triethylenemelamine" title="Triethylenemelamine">Triethylenemelamine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Platinum-based_antineoplastic" title="Platinum-based antineoplastic">Platinum-based</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Carboplatin" title="Carboplatin">Carboplatin</a><sup>#</sup></li> <li><a href="/wiki/Cisplatin" title="Cisplatin">Cisplatin</a><sup>#</sup></li> <li><a href="/wiki/Dicycloplatin" title="Dicycloplatin">Dicycloplatin</a></li> <li><a href="/wiki/Nedaplatin" title="Nedaplatin">Nedaplatin</a></li> <li><a href="/wiki/Oxaliplatin" title="Oxaliplatin">Oxaliplatin</a><sup>#</sup></li> <li><a href="/wiki/Satraplatin" title="Satraplatin">Satraplatin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Alkylating_antineoplastic_agent#Nonclassical" title="Alkylating antineoplastic agent">Nonclassical</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Altretamine" title="Altretamine">Altretamine</a></li> <li><i><a href="/wiki/Hydrazine" title="Hydrazine">Hydrazines</a></i> (<a href="/wiki/Procarbazine" title="Procarbazine">Procarbazine</a><sup>#</sup>)</li> <li><a href="/wiki/Etoglucid" title="Etoglucid">Etoglucid</a></li> <li><a href="/wiki/Mitobronitol" title="Mitobronitol">Mitobronitol</a></li> <li><a href="/wiki/Pipobroman" title="Pipobroman">Pipobroman</a></li> <li><i><a href="/wiki/Triazene" title="Triazene">Triazenes</a></i> (<a href="/wiki/Dacarbazine" title="Dacarbazine">Dacarbazine</a><sup>#</sup></li> <li><a href="/wiki/Mitozolomide" title="Mitozolomide">Mitozolomide</a><sup>§</sup></li> <li><a href="/wiki/Temozolomide" title="Temozolomide">Temozolomide</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Intercalation_(biochemistry)" title="Intercalation (biochemistry)">Intercalation</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Streptomyces" title="Streptomyces">Streptomyces</a> (<a href="/wiki/Dactinomycin" title="Dactinomycin">Dactinomycin</a><sup>#</sup></li> <li><a href="/wiki/Bleomycin" title="Bleomycin">Bleomycin</a><sup>#</sup></li> <li><a href="/wiki/Mitomycins" title="Mitomycins">Mitomycins</a></li> <li><a href="/wiki/Plicamycin" title="Plicamycin">Plicamycin</a>)</li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Photosensitizer" title="Photosensitizer">Photosensitizers</a>/<a href="/wiki/Photodynamic_therapy" title="Photodynamic therapy">PDT</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Aminolevulinic_acid" title="Aminolevulinic acid">Aminolevulinic acid</a></li> <li><a href="/wiki/Efaproxiral" title="Efaproxiral">Efaproxiral</a></li> <li><a href="/wiki/Methyl_aminolevulinate" title="Methyl aminolevulinate">Methyl aminolevulinate</a></li> <li><a href="/wiki/Padeliporfin" title="Padeliporfin">Padeliporfin</a></li> <li><i><a href="/wiki/Porphyrin" title="Porphyrin">Porphyrin derivatives</a></i> (<a href="/wiki/Porfimer_sodium" title="Porfimer sodium">Porfimer sodium</a></li> <li><a href="/wiki/Talaporfin" title="Talaporfin">Talaporfin</a></li> <li><a href="/wiki/Temoporfin" title="Temoporfin">Temoporfin</a></li> <li><a href="/wiki/Verteporfin" title="Verteporfin">Verteporfin</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Enzyme_inhibitor" title="Enzyme inhibitor">Enzyme inhibitors</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Farnesyltransferase_inhibitor" title="Farnesyltransferase inhibitor">FI</a></i> (<a href="/wiki/Tipifarnib" title="Tipifarnib">Tipifarnib</a><sup>§</sup>)</li> <li><i><a href="/wiki/Cyclin-dependent_kinase" title="Cyclin-dependent kinase">CDK</a> <a href="/wiki/Protein_kinase_inhibitor" title="Protein kinase inhibitor">inhibitors</a></i> (<a href="/wiki/Abemaciclib" title="Abemaciclib">Abemaciclib</a></li> <li><a href="/wiki/Alvocidib" title="Alvocidib">Alvocidib</a><sup>†</sup></li> <li><a href="/wiki/Palbociclib" title="Palbociclib">Palbociclib</a></li> <li><a href="/wiki/Ribociclib" title="Ribociclib">Ribociclib</a></li> <li><a href="/wiki/Seliciclib" title="Seliciclib">Seliciclib</a><sup>†</sup>)</li> <li><i><a href="/wiki/Proteasome_inhibitor" title="Proteasome inhibitor">PrI</a></i> <ul><li><a href="/wiki/Bortezomib" title="Bortezomib">Bortezomib</a></li> <li><a href="/wiki/Carfilzomib" title="Carfilzomib">Carfilzomib</a></li> <li><a href="/wiki/Oprozomib" title="Oprozomib">Oprozomib</a></li> <li><a href="/wiki/Ixazomib" title="Ixazomib">Ixazomib</a></li></ul></li> <li><i><a href="/wiki/Phosphodiesterase_inhibitor" title="Phosphodiesterase inhibitor">PhI</a></i> (<a href="/wiki/Anagrelide" title="Anagrelide">Anagrelide</a>)</li> <li><i><a href="/wiki/IMP_dehydrogenase" class="mw-redirect" title="IMP dehydrogenase">IMPDI</a></i> (<a href="/wiki/Tiazofurin" title="Tiazofurin">Tiazofurin</a><sup>§</sup>)</li> <li><i><a href="/wiki/Lipoxygenase_inhibitor" class="mw-redirect" title="Lipoxygenase inhibitor">LI</a></i> (<a href="/wiki/Masoprocol" title="Masoprocol">Masoprocol</a>)</li> <li><i><a href="/wiki/PARP_inhibitor" title="PARP inhibitor">PARP inhibitor</a></i> (<a href="/wiki/Fuzuloparib" title="Fuzuloparib">Fuzuloparib</a></li> <li><a href="/wiki/Niraparib" title="Niraparib">Niraparib</a> <a href="/wiki/Niraparib/abiraterone_acetate" title="Niraparib/abiraterone acetate">+abiraterone acetate</a></li> <li><a href="/wiki/Olaparib" title="Olaparib">Olaparib</a></li> <li><a href="/wiki/Rucaparib" title="Rucaparib">Rucaparib</a>)</li> <li><i><a href="/wiki/Histone_deacetylase_inhibitor" title="Histone deacetylase inhibitor">HDAC</a></i> (<a href="/wiki/Belinostat" title="Belinostat">Belinostat</a></li> <li><a href="/wiki/Entinostat" title="Entinostat">Entinostat</a></li> <li><a href="/wiki/Panobinostat" title="Panobinostat">Panobinostat</a></li> <li><a href="/wiki/Romidepsin" title="Romidepsin">Romidepsin</a></li> <li><a href="/wiki/Vorinostat" title="Vorinostat">Vorinostat</a>)</li> <li><i><a href="/wiki/Phosphoinositide_3-kinase_inhibitor" title="Phosphoinositide 3-kinase inhibitor">PIKI</a> (Pi3K)</i> (<a href="/wiki/Alpelisib" title="Alpelisib">Alpelisib</a></li> <li><a href="/wiki/Copanlisib" title="Copanlisib">Copanlisib</a><sup>‡</sup></li> <li><a href="/wiki/Duvelisib" title="Duvelisib">Duvelisib</a></li> <li><a href="/wiki/Idelalisib" title="Idelalisib">Idelalisib</a></li> <li><a href="/wiki/Inavolisib" title="Inavolisib">Inavolisib</a></li> <li><a href="/wiki/Umbralisib" title="Umbralisib">Umbralisib</a><sup>‡</sup>)</li> <li><i><a href="/wiki/Isocitrate_dehydrogenase" title="Isocitrate dehydrogenase">IDH</a></i> (<a href="/wiki/Enasidenib" title="Enasidenib">Enasidenib</a></li> <li><a href="/wiki/Ivosidenib" title="Ivosidenib">Ivosidenib</a></li> <li><a href="/wiki/Olutasidenib" title="Olutasidenib">Olutasidenib</a></li> <li><a href="/wiki/Vorasidenib" title="Vorasidenib">Vorasidenib</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Receptor_antagonist" title="Receptor antagonist">Receptor antagonists</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Endothelin_receptor_antagonist" title="Endothelin receptor antagonist">ERA</a></i> (<a href="/wiki/Atrasentan" title="Atrasentan">Atrasentan</a>)</li> <li><i><a href="/wiki/Retinoid_X_receptor" title="Retinoid X receptor">Retinoid X receptor</a></i> (<a href="/wiki/Bexarotene" title="Bexarotene">Bexarotene</a>)</li> <li><i><a href="/wiki/Sex_steroid" class="mw-redirect" title="Sex steroid">Sex steroid</a></i> (<a href="/wiki/Testolactone" title="Testolactone">Testolactone</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other/ungrouped</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adagrasib" title="Adagrasib">Adagrasib</a></li> <li><a href="/wiki/Aflibercept" title="Aflibercept">Aflibercept</a></li> <li><a href="/wiki/Arsenic_trioxide" title="Arsenic trioxide">Arsenic trioxide</a></li> <li><i><a href="/wiki/Asparagine" title="Asparagine">Asparagine depleters</a></i> (<a href="/wiki/Asparaginase" title="Asparaginase">Asparaginase</a><sup>#</sup>/<a href="/wiki/Pegaspargase" title="Pegaspargase">Pegaspargase</a>)</li> <li><a href="/wiki/Axicabtagene_ciloleucel" title="Axicabtagene ciloleucel">Axicabtagene ciloleucel</a></li> <li><a href="/wiki/Belzutifan" title="Belzutifan">Belzutifan</a></li> <li><a href="/wiki/Bexarotene" title="Bexarotene">Bexarotene</a></li> <li><a href="/wiki/Brexucabtagene_autoleucel" title="Brexucabtagene autoleucel">Brexucabtagene autoleucel</a></li> <li><a href="/wiki/Celecoxib" title="Celecoxib">Celecoxib</a></li> <li><a href="/wiki/Ciltacabtagene_autoleucel" title="Ciltacabtagene autoleucel">Ciltacabtagene autoleucel</a></li> <li><a href="/wiki/Demecolcine" title="Demecolcine">Demecolcine</a></li> <li><a href="/wiki/Denileukin_diftitox" title="Denileukin diftitox">Denileukin diftitox</a></li> <li><a href="/wiki/Eflornithine" title="Eflornithine">Eflornithine</a></li> <li><a href="/wiki/Elesclomol" title="Elesclomol">Elesclomol</a><sup>§</sup></li> <li><a href="/wiki/Elsamitrucin" title="Elsamitrucin">Elsamitrucin</a></li> <li><a href="/wiki/Epacadostat" title="Epacadostat">Epacadostat</a></li> <li><a href="/wiki/Eribulin" title="Eribulin">Eribulin</a></li> <li><a href="/wiki/Estramustine_phosphate" title="Estramustine phosphate">Estramustine</a></li> <li><a href="/wiki/Glasdegib" title="Glasdegib">Glasdegib</a></li> <li><a href="/wiki/Idecabtagene_vicleucel" title="Idecabtagene vicleucel">Idecabtagene vicleucel</a></li> <li><a href="/wiki/Imetelstat" title="Imetelstat">Imetelstat</a></li> <li><a href="/wiki/Lifileucel" title="Lifileucel">Lifileucel</a></li> <li><a href="/wiki/Lisocabtagene_maraleucel" title="Lisocabtagene maraleucel">Lisocabtagene maraleucel</a></li> <li><a href="/wiki/Lonidamine" title="Lonidamine">Lonidamine</a></li> <li><a href="/wiki/Lucanthone" title="Lucanthone">Lucanthone</a></li> <li><a href="/wiki/Lurbinectedin" title="Lurbinectedin">Lurbinectedin</a></li> <li><a href="/wiki/Mitoguazone" title="Mitoguazone">Mitoguazone</a></li> <li><a href="/wiki/Mitotane" title="Mitotane">Mitotane</a></li> <li><a href="/wiki/Nadofaragene_firadenovec" title="Nadofaragene firadenovec">Nadofaragene firadenovec</a></li> <li><a href="/wiki/Navitoclax" title="Navitoclax">Navitoclax</a></li> <li><a href="/wiki/Obecabtagene_autoleucel" title="Obecabtagene autoleucel">Obecabtagene autoleucel</a></li> <li><a href="/wiki/Oblimersen" title="Oblimersen">Oblimersen</a><sup>†</sup></li> <li><a href="/wiki/Omacetaxine_mepesuccinate" title="Omacetaxine mepesuccinate">Omacetaxine mepesuccinate</a></li> <li><a href="/wiki/Plitidepsin" title="Plitidepsin">Plitidepsin</a></li> <li><a href="/wiki/Tabelecleucel" title="Tabelecleucel">Tabelecleucel</a></li> <li><i><a href="/wiki/Retinoid" title="Retinoid">Retinoids</a></i> (<a href="/wiki/Alitretinoin" title="Alitretinoin">Alitretinoin</a></li> <li><a href="/wiki/Tretinoin" title="Tretinoin">Tretinoin</a><sup>#</sup>)</li> <li><a href="/wiki/Selinexor" title="Selinexor">Selinexor</a></li> <li><a href="/w/index.php?title=Sitimagene_ceradenovec&action=edit&redlink=1" class="new" title="Sitimagene ceradenovec (page does not exist)">Sitimagene ceradenovec</a></li> <li><a href="/wiki/Sotorasib" title="Sotorasib">Sotorasib</a></li> <li><a href="/wiki/Tagraxofusp" title="Tagraxofusp">Tagraxofusp</a></li> <li><a href="/wiki/Talimogene_laherparepvec" title="Talimogene laherparepvec">Talimogene laherparepvec</a></li> <li><a href="/wiki/Tazemetostat" title="Tazemetostat">Tazemetostat</a></li> <li><a href="/wiki/Tebentafusp" title="Tebentafusp">Tebentafusp</a></li> <li><a href="/wiki/Tiazofurine" class="mw-redirect" title="Tiazofurine">Tiazofurine</a></li> <li><a href="/wiki/Tigilanol_tiglate" title="Tigilanol tiglate">Tigilanol tiglate</a></li> <li><a href="/wiki/Tisagenlecleucel" title="Tisagenlecleucel">Tisagenlecleucel</a></li> <li><a href="/wiki/Trabectedin" title="Trabectedin">Trabectedin</a></li> <li><a href="/wiki/Veliparib" title="Veliparib">Veliparib</a></li> <li><a href="/wiki/Venetoclax" title="Venetoclax">Venetoclax</a></li> <li><a href="/w/index.php?title=Verdinexor&action=edit&redlink=1" class="new" title="Verdinexor (page does not exist)">Verdinexor</a></li> <li><a href="/wiki/Vosaroxin" title="Vosaroxin">Vosaroxin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><td class="navbox-abovebelow" colspan="2" style="padding: 0px;"><div><div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Immunosuppressive_drugs_/_Immunosuppressants_(L04)180" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Immunosuppressants" title="Template:Immunosuppressants"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Immunosuppressants" title="Template talk:Immunosuppressants"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Immunosuppressants" title="Special:EditPage/Template:Immunosuppressants"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Immunosuppressive_drugs_/_Immunosuppressants_(L04)180" style="font-size:114%;margin:0 4em"><a href="/wiki/Immunosuppressive_drug" title="Immunosuppressive drug">Immunosuppressive drugs</a> / <a href="/wiki/Immunosuppression" title="Immunosuppression">Immunosuppressants</a> (<a href="/wiki/ATC_code_L04" title="ATC code L04">L04</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Intracellular<br />(initiation)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Antimetabolite" title="Antimetabolite">Antimetabolites</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Purine_synthesis_inhibitor" class="mw-redirect" title="Purine synthesis inhibitor">purine synthesis inhibitors</a></i> <ul><li><a href="/wiki/Azathioprine" title="Azathioprine">Azathioprine</a></li> <li><a href="/wiki/Mycophenolic_acid" title="Mycophenolic acid">Mycophenolic acid</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Dihydroorotate_dehydrogenase" title="Dihydroorotate dehydrogenase">dihydroorotate dehydrogenase</a></i> inhibitors <ul><li><a href="/wiki/Leflunomide" title="Leflunomide">Leflunomide</a></li> <li><a href="/wiki/Teriflunomide" title="Teriflunomide">Teriflunomide</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Antifolate" title="Antifolate">antifolate</a></i> <ul><li><a href="/wiki/Methotrexate" title="Methotrexate">Methotrexate</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Macrolide" title="Macrolide">Macrolides</a>/<br />other <a href="/wiki/Interleukin_2" title="Interleukin 2">IL-2</a> inhibitors</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/FKBP" title="FKBP">FKBP</a>/<a href="/wiki/Cyclophilin" title="Cyclophilin">Cyclophilin</a>/<a href="/wiki/Calcineurin" title="Calcineurin">Calcineurin</a></i> <ul><li><a href="/wiki/Ciclosporin" title="Ciclosporin">Ciclosporin</a></li> <li><a href="/wiki/Pimecrolimus" title="Pimecrolimus">Pimecrolimus</a></li> <li><a href="/wiki/Tacrolimus" title="Tacrolimus">Tacrolimus</a></li> <li><a href="/wiki/Voclosporin" title="Voclosporin">Voclosporin</a></li></ul></li></ul> <ul><li><a href="/wiki/Abetimus" title="Abetimus">Abetimus</a></li> <li><a href="/wiki/Gusperimus" title="Gusperimus">Gusperimus</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Immunomodulatory_imide_drug" class="mw-redirect" title="Immunomodulatory imide drug">IMiDs</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Lenalidomide" title="Lenalidomide">Lenalidomide</a></li> <li><a href="/wiki/Pomalidomide" title="Pomalidomide">Pomalidomide</a></li> <li><a href="/wiki/Thalidomide" title="Thalidomide">Thalidomide</a></li> <li><i><a href="/wiki/PDE4_inhibitor" title="PDE4 inhibitor">PDE4 inhibitor</a></i> <ul><li><a href="/wiki/Apremilast" title="Apremilast">Apremilast</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Intracellular<br />(reception)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Interleukin_1_receptor_antagonist" class="mw-redirect" title="Interleukin 1 receptor antagonist">IL-1 receptor antagonists</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Anakinra" title="Anakinra">Anakinra</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/MTOR" title="MTOR">mTOR</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Everolimus" title="Everolimus">Everolimus</a></li> <li><a href="/wiki/Ridaforolimus" title="Ridaforolimus">Ridaforolimus</a></li> <li><a href="/wiki/Sirolimus" title="Sirolimus">Sirolimus</a></li> <li><a href="/wiki/Temsirolimus" title="Temsirolimus">Temsirolimus</a></li> <li><a href="/wiki/Umirolimus" title="Umirolimus">Umirolimus</a></li> <li><a href="/wiki/Zotarolimus" title="Zotarolimus">Zotarolimus</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Extracellular</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Antibody" title="Antibody">Antibodies</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Monoclonal_antibody" title="Monoclonal antibody">Monoclonal</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Serum target<br />(noncellular)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Complement_component_5" title="Complement component 5">Complement component 5</a></i> <ul><li><a href="/wiki/Eculizumab" title="Eculizumab">Eculizumab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/TNF_inhibitor" title="TNF inhibitor">TNF</a></i> <ul><li><a href="/wiki/Adalimumab" title="Adalimumab">Adalimumab</a></li> <li><a href="/wiki/Afelimomab" title="Afelimomab">Afelimomab</a></li> <li><a href="/wiki/Certolizumab_pegol" title="Certolizumab pegol">Certolizumab pegol</a></li> <li><a href="/wiki/Golimumab" title="Golimumab">Golimumab</a></li> <li><a href="/wiki/Infliximab" title="Infliximab">Infliximab</a></li> <li><a href="/wiki/Nerelimomab" title="Nerelimomab">Nerelimomab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Interleukin" title="Interleukin">Interleukin</a></i> <ul><li><a href="/wiki/Anakinra" title="Anakinra">Anakinra</a></li> <li><a href="/wiki/Basiliximab" title="Basiliximab">Basiliximab</a></li> <li><a href="/wiki/Bimekizumab" title="Bimekizumab">Bimekizumab</a></li> <li><a href="/wiki/Briakinumab" title="Briakinumab">Briakinumab</a></li> <li><a href="/wiki/Brodalumab" title="Brodalumab">Brodalumab</a></li> <li><a href="/wiki/Canakinumab" title="Canakinumab">Canakinumab</a></li> <li><a href="/wiki/Daclizumab" title="Daclizumab">Daclizumab</a></li> <li><a href="/wiki/Guselkumab" title="Guselkumab">Guselkumab</a></li> <li><a href="/wiki/Ixekizumab" title="Ixekizumab">Ixekizumab</a></li> <li><a href="/w/index.php?title=Netakimab&action=edit&redlink=1" class="new" title="Netakimab (page does not exist)">Netakimab</a></li> <li><a href="/wiki/Olokizumab" title="Olokizumab">Olokizumab</a></li> <li><a href="/wiki/Rilonacept" title="Rilonacept">Rilonacept</a></li> <li><a href="/wiki/Risankizumab" title="Risankizumab">Risankizumab</a></li> <li><a href="/wiki/Sarilumab" title="Sarilumab">Sarilumab</a></li> <li><a href="/wiki/Satralizumab" title="Satralizumab">Satralizumab</a></li> <li><a href="/wiki/Secukinumab" title="Secukinumab">Secukinumab</a></li> <li><a href="/wiki/Siltuximab" title="Siltuximab">Siltuximab</a></li> <li><a href="/wiki/Sirukumab" title="Sirukumab">Sirukumab</a></li> <li><a href="/wiki/Spesolimab" title="Spesolimab">Spesolimab</a></li> <li><a href="/wiki/Tildrakizumab" title="Tildrakizumab">Tildrakizumab</a></li> <li><a href="/wiki/Tocilizumab" title="Tocilizumab">Tocilizumab</a></li> <li><a href="/wiki/Ustekinumab" title="Ustekinumab">Ustekinumab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Interleukin_5" title="Interleukin 5">Interleukin 5</a></i> <ul><li><a href="/wiki/Mepolizumab" title="Mepolizumab">Mepolizumab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Immunoglobulin_E" title="Immunoglobulin E">Immunoglobulin E</a></i> <ul><li><a href="/wiki/Omalizumab" title="Omalizumab">Omalizumab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Interferon" title="Interferon">Interferon</a></i> <ul><li><a href="/wiki/Faralimomab" title="Faralimomab">Faralimomab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Interleukin_6" title="Interleukin 6">IL-6</a></i> <ul><li><a href="/wiki/Elsilimomab" title="Elsilimomab">Elsilimomab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Interleukin_12" title="Interleukin 12">IL-12</a>, <a href="/wiki/Interleukin_13" title="Interleukin 13">IL-13</a>, and <a href="/wiki/Interleukin_23" title="Interleukin 23">IL-23</a></i> <ul><li><a href="/wiki/Lebrikizumab" title="Lebrikizumab">Lebrikizumab</a></li> <li><a href="/wiki/Ustekinumab" title="Ustekinumab">Ustekinumab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Interleukin_17" title="Interleukin 17">IL-17A</a></i> <ul><li><a href="/wiki/Secukinumab" title="Secukinumab">Secukinumab</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Cellular<br />target</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/CD3_(immunology)" title="CD3 (immunology)">CD3</a></i> <ul><li><a href="/wiki/Muromonab-CD3" title="Muromonab-CD3">Muromonab-CD3</a></li> <li><a href="/wiki/Otelixizumab" title="Otelixizumab">Otelixizumab</a></li> <li><a href="/wiki/Teplizumab" title="Teplizumab">Teplizumab</a></li> <li><a href="/wiki/Visilizumab" title="Visilizumab">Visilizumab</a></li></ul></li> <li><i><a href="/wiki/CD4" title="CD4">CD4</a></i> <ul><li><a href="/wiki/Clenoliximab" title="Clenoliximab">Clenoliximab</a></li> <li><a href="/wiki/Keliximab" title="Keliximab">Keliximab</a></li> <li><a href="/wiki/Zanolimumab" title="Zanolimumab">Zanolimumab</a></li></ul></li> <li><i><a href="/wiki/CD11a" class="mw-redirect" title="CD11a">CD11a</a></i> <ul><li><a href="/wiki/Efalizumab" title="Efalizumab">Efalizumab</a></li></ul></li> <li><i><a href="/wiki/CD18" class="mw-redirect" title="CD18">CD18</a></i> <ul><li><a href="/wiki/Erlizumab" title="Erlizumab">Erlizumab</a></li></ul></li> <li><i><a href="/wiki/CD20" title="CD20">CD20</a></i> <ul><li><a href="/wiki/Obinutuzumab" title="Obinutuzumab">Obinutuzumab</a></li> <li><a href="/wiki/Ocrelizumab" title="Ocrelizumab">Ocrelizumab</a> (<a href="/wiki/Ocrelizumab/hyaluronidase" title="Ocrelizumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Pascolizumab" title="Pascolizumab">Pascolizumab</a></li> <li><a href="/wiki/Rituximab" title="Rituximab">Rituximab</a></li> <li><a href="/wiki/Ublituximab" title="Ublituximab">Ublituximab</a></li></ul></li> <li><i><a href="/wiki/CD23" title="CD23">CD23</a></i> <ul><li><a href="/wiki/Gomiliximab" class="mw-redirect" title="Gomiliximab">Gomiliximab</a></li> <li><a href="/wiki/Lumiliximab" title="Lumiliximab">Lumiliximab</a></li></ul></li> <li><i><a href="/wiki/CD40_(protein)" title="CD40 (protein)">CD40</a></i> <ul><li><a href="/wiki/Teneliximab" title="Teneliximab">Teneliximab</a></li> <li><a href="/wiki/Toralizumab" title="Toralizumab">Toralizumab</a></li></ul></li> <li><i><a href="/wiki/L-selectin" title="L-selectin">CD62L/L-selectin</a></i> <ul><li><a href="/wiki/Aselizumab" title="Aselizumab">Aselizumab</a></li></ul></li> <li><i><a href="/wiki/CD80" title="CD80">CD80</a></i> <ul><li><a href="/wiki/Galiximab" title="Galiximab">Galiximab</a></li></ul></li> <li><i><a href="/wiki/Basigin" title="Basigin">CD147/Basigin</a></i> <ul><li><a href="/wiki/Gavilimomab" title="Gavilimomab">Gavilimomab</a></li></ul></li> <li><i><a href="/wiki/CD154" title="CD154">CD154</a></i> <ul><li><a href="/wiki/Frexalimab" title="Frexalimab">Frexalimab</a></li> <li><a href="/wiki/Ruplizumab" title="Ruplizumab">Ruplizumab</a></li></ul></li></ul> <ul><li><i>BLyS</i> <ul><li><a href="/wiki/Belimumab" title="Belimumab">Belimumab</a></li></ul></li> <li><i><a href="/wiki/Chloramphenicol_acetyltransferase" title="Chloramphenicol acetyltransferase">CAT</a></i> <ul><li><a href="/wiki/Bertilimumab" title="Bertilimumab">Bertilimumab</a></li> <li><a href="/wiki/Lerdelimumab" title="Lerdelimumab">Lerdelimumab</a></li> <li><a href="/wiki/Metelimumab" title="Metelimumab">Metelimumab</a></li></ul></li> <li><i><a href="/wiki/Integrin" title="Integrin">Integrin</a></i> <ul><li><a href="/wiki/Natalizumab" title="Natalizumab">Natalizumab</a></li> <li><a href="/wiki/Vedolizumab" title="Vedolizumab">Vedolizumab</a></li></ul></li> <li><i><a href="/wiki/Interleukin-6_receptor" title="Interleukin-6 receptor">Interleukin-6 receptor</a></i> <ul><li><a href="/wiki/Tocilizumab" title="Tocilizumab">Tocilizumab</a></li></ul></li> <li><i><a href="/wiki/Lymphocyte_function-associated_antigen_1" title="Lymphocyte function-associated antigen 1">LFA-1</a></i> <ul><li><a href="/wiki/Odulimomab" title="Odulimomab">Odulimomab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/IL-2_receptor" title="IL-2 receptor">IL-2 receptor/CD25</a></i> <ul><li><a href="/wiki/Basiliximab" title="Basiliximab">Basiliximab</a></li> <li><a href="/wiki/Daclizumab" title="Daclizumab">Daclizumab</a></li> <li><a href="/wiki/Inolimomab" title="Inolimomab">Inolimomab</a></li></ul></li></ul> <ul><li><i><a href="/wiki/T_cell" title="T cell">T-lymphocyte</a></i> (<a href="/wiki/Zolimomab_aritox" title="Zolimomab aritox">Zolimomab aritox</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Unsorted</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Alemtuzumab" title="Alemtuzumab">Alemtuzumab</a></li> <li><a href="/wiki/Anifrolumab" title="Anifrolumab">Anifrolumab</a></li> <li><a href="/wiki/Atorolimumab" title="Atorolimumab">Atorolimumab</a></li> <li><a href="/w/index.php?title=Begelomab&action=edit&redlink=1" class="new" title="Begelomab (page does not exist)">Begelomab</a></li> <li><a href="/wiki/Cedelizumab" title="Cedelizumab">Cedelizumab</a></li> <li><a href="/wiki/Emapalumab" title="Emapalumab">Emapalumab</a></li> <li><a href="/wiki/Fontolizumab" title="Fontolizumab">Fontolizumab</a></li> <li><a href="/wiki/Inebilizumab" title="Inebilizumab">Inebilizumab</a></li> <li><a href="/wiki/Maslimomab" title="Maslimomab">Maslimomab</a></li> <li><a href="/wiki/Morolimumab" title="Morolimumab">Morolimumab</a></li> <li><a href="/wiki/Ofatumumab" title="Ofatumumab">Ofatumumab</a></li> <li><a href="/wiki/Pexelizumab" title="Pexelizumab">Pexelizumab</a></li> <li><a href="/wiki/Reslizumab" title="Reslizumab">Reslizumab</a></li> <li><a href="/wiki/Rovelizumab" title="Rovelizumab">Rovelizumab</a></li> <li><a href="/wiki/Siplizumab" title="Siplizumab">Siplizumab</a></li> <li><a href="/wiki/Talizumab" title="Talizumab">Talizumab</a></li> <li><a href="/wiki/Telimomab_aritox" title="Telimomab aritox">Telimomab aritox</a></li> <li><a href="/wiki/Teprotumumab" title="Teprotumumab">Teprotumumab</a></li> <li><a href="/wiki/Vapaliximab" title="Vapaliximab">Vapaliximab</a></li> <li><a href="/wiki/Vepalimomab" title="Vepalimomab">Vepalimomab</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Polyclonal_antibodies" title="Polyclonal antibodies">Polyclonal</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Anti-thymocyte_globulin" title="Anti-thymocyte globulin">Anti-thymocyte globulin</a></li> <li><a href="/wiki/Anti-lymphocyte_globulin" title="Anti-lymphocyte globulin">Anti-lymphocyte globulin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">-cept (<a href="/wiki/Fusion_protein" title="Fusion protein">Fusion</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA-4</a></i> <ul><li><a href="/wiki/Abatacept" title="Abatacept">Abatacept</a></li> <li><a href="/wiki/Belatacept" title="Belatacept">Belatacept</a></li></ul></li> <li><i><a href="/wiki/TNF_inhibitor" title="TNF inhibitor">TNF inhibitor</a></i> <ul><li><a href="/wiki/Etanercept" title="Etanercept">Etanercept</a></li> <li><a href="/w/index.php?title=Opinercept&action=edit&redlink=1" class="new" title="Opinercept (page does not exist)">Opinercept</a></li></ul></li> <li><a href="/wiki/Aflibercept" title="Aflibercept">Aflibercept</a></li> <li><a href="/wiki/Alefacept" title="Alefacept">Alefacept</a></li> <li><a href="/wiki/Rilonacept" title="Rilonacept">Rilonacept</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Unsorted</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Avacopan" title="Avacopan">Avacopan</a></li> <li><a href="/wiki/Baricitinib" title="Baricitinib">Baricitinib</a></li> <li><a href="/wiki/Bimekizumab" title="Bimekizumab">Bimekizumab</a></li> <li><a href="/wiki/Blisibimod" title="Blisibimod">Blisibimod</a></li> <li><a href="/wiki/Briakinumab" title="Briakinumab">Briakinumab</a></li> <li><a href="/wiki/Brodalumab" title="Brodalumab">Brodalumab</a></li> <li><a href="/wiki/Canakinumab" title="Canakinumab">Canakinumab</a></li> <li><a href="/wiki/Crovalimab" title="Crovalimab">Crovalimab</a></li> <li><a href="/wiki/Danicopan" title="Danicopan">Danicopan</a></li> <li><a href="/wiki/Darvadstrocel" title="Darvadstrocel">Darvadstrocel</a></li> <li><a href="/wiki/Deucravacitinib" title="Deucravacitinib">Deucravacitinib</a></li> <li><a href="/wiki/Deuruxolitinib" title="Deuruxolitinib">Deuruxolitinib</a></li> <li><a href="/wiki/Dimethyl_fumarate" title="Dimethyl fumarate">Dimethyl fumarate</a></li> <li><a href="/wiki/Diroximel_fumarate" title="Diroximel fumarate">Diroximel fumarate</a></li> <li><a href="/wiki/Efgartigimod_alfa" title="Efgartigimod alfa">Efgartigimod alfa</a> (<a href="/wiki/Efgartigimod_alfa/hyaluronidase" title="Efgartigimod alfa/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Etrasimod" title="Etrasimod">Etrasimod</a></li> <li><a href="/wiki/Filgotinib" title="Filgotinib">Filgotinib</a></li> <li><a href="/wiki/Fingolimod" title="Fingolimod">Fingolimod</a></li> <li><a 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