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</div> </div> </div> </a></div></div> <div class="slideshow-controls"> <div class="slideshow-controls__arrows"></div> </div> <span class="product-label-list"><script id="variant-label-8029679059112-45599343870120" type="text/template"></script><div class="product-label-container"></div></span> </div> <div class="title-row" > <h1 class="title">Non-CYP reaction phenotyping</h1> </div> <div class="" > <div class="product-description rte cf"><div id="formula-bar-name-box-wrapper" class="name-box-enabled formula-bar-with-name-box-wrapper" data-mce-fragment="1"> <div id="formula-bar" class="formula-bar formulabar-disabled" data-mce-fragment="1"> <div id="t-formula-bar-input-container" data-mce-fragment="1"> <div dir="ltr" data-mce-fragment="1"> <div spellcheck="false" id="t-formula-bar-input" data-mce-fragment="1"> <div class="cell-input disabled-input" role="combobox" dir="ltr" aria-autocomplete="list" tabindex="0" data-mce-fragment="1" data-mce-tabindex="0" contenteditable="false" docs-unhandledkeys=""> <span data-mce-fragment="1">The non-CYP mediated metabolism of the compound is investigated using various recombinant enzymes and/or human liver cytosol with enzyme-selective inhibitors. The collected samples are analyzed by UPLC/HR-MS to measure the stability of the compounds.</span><br data-mce-fragment="1"> </div> </div> </div> </div> </div> </div></div> </div> <div class="product-detail-accordion not-in-quickbuy" > <div class="cc-accordion" data-allow-multi-open="true"> <details class="cc-accordion-item is-open" open> <summary class="cc-accordion-item__title"><div class="with-icon"> <span class="material-symbols-outlined"> check </span> <span class="with-icon__beside">Protocol</span> </div></summary> <div class="cc-accordion-item__panel"> <div class="cc-accordion-item__content rte cf"><p>Test concentrations: 1</p><p>Time points: 5</p><p>Replicates: 3</p><p>Positive controls</p><p>UPLC/HR-MS analysis</p></div> </div> </details> </div> </div> <div class="product-detail-accordion not-in-quickbuy" > <div class="cc-accordion" data-allow-multi-open="true"> <details class="cc-accordion-item is-open" open> <summary class="cc-accordion-item__title"><div class="with-icon"> <span class="material-symbols-outlined"> check </span> <span class="with-icon__beside">Deliverables</span> </div></summary> <div class="cc-accordion-item__panel"> <div class="cc-accordion-item__content rte cf"><p><span class="metafield-multi_line_text_field">Involvement of the enzymes in the metabolism of the compound based on substrate depletion and metabolite formation<br /> </span></p></div> </div> </details> </div> </div> <div class="product-detail-accordion not-in-quickbuy" > <div class="cc-accordion" data-allow-multi-open="true"> <details class="cc-accordion-item is-open" open> <summary class="cc-accordion-item__title"><div class="with-icon"> <span class="material-symbols-outlined"> check </span> <span class="with-icon__beside">Reporting</span> </div></summary> <div class="cc-accordion-item__panel"> <div class="cc-accordion-item__content rte cf"><p><span class="metafield-multi_line_text_field">Full Word/PDF report<br /> </span></p></div> </div> </details> </div> </div> <div class="product-detail-accordion not-in-quickbuy" > <div class="cc-accordion" data-allow-multi-open="true"> <details class="cc-accordion-item"> <summary class="cc-accordion-item__title">Background</summary> <div class="cc-accordion-item__panel"> <div class="cc-accordion-item__content rte cf"><p>Enzyme phenotyping provides information on the enzymes involved in the metabolism of a new chemical entity, which is needed to evaluate the drug interaction vulnerability of the compound as a “victim-drug”. The phenotyping of metabolizing enzymes is also needed to evaluate the risk for highly variable clearance between individuals or populations due to the involvement of enzymes with high degree of polymorphism. A thorough evaluation of metabolizing enzymes also requires metabolite identification. The most common approach for enzyme identification is the use of recombinant enzymes and extrapolation of the results based on the in vivo protein levels, and the use of liver microsomal incubations together with cytochrome P450 (CYP)-selective inhibitors under linear metabolite formation kinetics. In both methods, monitoring of metabolite formation is clearly more reliable than monitoring substrate depletion only, although the latter is often used for high throughput evaluation. The clever use of HR-MS technology allows metabolite monitoring later on from the very same LC/MS data, even if only substrate depletion was analyzed in the first place. If CYP-focused enzyme phenotyping assays do not show clear results, non-CYP mediated metabolism should be studied and the enzymes involved in the metabolic processes identified. This can be done by using recombinant enzymes, such as UDP glucuronosyltransferases (UGT), sulfotransferases (SULT), N-acetyltransferases (NAT), flavin containing mono-oxygenases (FMO), monoamine-oxidases (MAO), carboxylesterases (CE), or aldehyde dehydrogenase (ALDH). Metabolism via aldehyde oxidase (AOX), xanthine oxidase (XO), aldo-keto reductase (AKR) and carbonyl reductase (CR) can be investigated by using human liver cytosol with enzyme-selective inhibitors. For more thorough evaluation of in vivo role of each enzyme, evaluation of kinetic parameters Vmax and Km with different enzymes would be advisable.</p></div> </div> </details> </div> </div> </div> </div> <div class="detail product-column-right" data-cc-animate data-cc-animate-delay="0.2s"> <div class="product-form" data-ajax-add-to-cart="true" data-product-id="8029679059112" data-enable-history-state="true"> <div class="buy-buttons-row" > <form method="post" action="/cart/add" id="product-form-template--16460963283112__main-8029679059112" accept-charset="UTF-8" class="form product-purchase-form" enctype="multipart/form-data" data-product-id="8029679059112"><input type="hidden" name="form_type" value="product" /><input type="hidden" name="utf8" value="✓" /> <select name="id" class="original-selector hidden" aria-label="Options"> <option value="45599343870120" selected="selected" data-stock="">Default Title</option> </select> <div class="quantity-submit-row input-row "> <div class="quantity-submit-row__submit input-row"><button class="button button--large" type="submit" data-add-to-cart-text="Add to quote request">Add to quote request</button> </div> </div> <input type="hidden" name="product-id" value="8029679059112" /><input type="hidden" name="section-id" value="template--16460963283112__main" /></form> </div> <div class="lightish-spaced-row-above only-in-quickbuy"> <a class="more" href="/products/non-cyp-reaction-phenotyping"> <span class="beside-svg underline">More details</span> <span class="icon--small icon-natcol ltr-icon"> <span class="material-symbols-outlined"> chevron_right </span></span> </a> </div> </div> <script type="application/json" id="ProductJson-8029679059112">{"id":8029679059112,"title":"Non-CYP reaction phenotyping","handle":"non-cyp-reaction-phenotyping","description":"\u003cdiv id=\"formula-bar-name-box-wrapper\" class=\"name-box-enabled formula-bar-with-name-box-wrapper\" data-mce-fragment=\"1\"\u003e\n\u003cdiv id=\"formula-bar\" class=\"formula-bar formulabar-disabled\" data-mce-fragment=\"1\"\u003e\n\u003cdiv id=\"t-formula-bar-input-container\" data-mce-fragment=\"1\"\u003e\n\u003cdiv dir=\"ltr\" data-mce-fragment=\"1\"\u003e\n\u003cdiv spellcheck=\"false\" id=\"t-formula-bar-input\" data-mce-fragment=\"1\"\u003e\n\u003cdiv class=\"cell-input disabled-input\" role=\"combobox\" dir=\"ltr\" aria-autocomplete=\"list\" tabindex=\"0\" data-mce-fragment=\"1\" data-mce-tabindex=\"0\" contenteditable=\"false\" docs-unhandledkeys=\"\"\u003e\n\u003cspan data-mce-fragment=\"1\"\u003eThe non-CYP mediated metabolism of the compound is investigated using various recombinant enzymes and\/or human liver cytosol with enzyme-selective inhibitors. The collected samples are analyzed by UPLC\/HR-MS to measure the stability of the compounds.\u003c\/span\u003e\u003cbr data-mce-fragment=\"1\"\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e","published_at":"2023-11-06T16:39:27+02:00","created_at":"2023-11-06T16:39:27+02:00","vendor":"Admescope","type":"","tags":[],"price":0,"price_min":0,"price_max":0,"available":true,"price_varies":false,"compare_at_price":null,"compare_at_price_min":0,"compare_at_price_max":0,"compare_at_price_varies":false,"variants":[{"id":45599343870120,"title":"Default Title","option1":"Default Title","option2":null,"option3":null,"sku":"","requires_shipping":false,"taxable":true,"featured_image":null,"available":true,"name":"Non-CYP reaction phenotyping","public_title":null,"options":["Default Title"],"price":0,"weight":0,"compare_at_price":null,"inventory_management":null,"barcode":"","requires_selling_plan":false,"selling_plan_allocations":[]}],"images":["\/\/admeshop.com\/cdn\/shop\/files\/InvitrometabolismNEG_c1fb323d-7298-4679-98cb-f3acae264649.png?v=1702464133"],"featured_image":"\/\/admeshop.com\/cdn\/shop\/files\/InvitrometabolismNEG_c1fb323d-7298-4679-98cb-f3acae264649.png?v=1702464133","options":["Title"],"media":[{"alt":null,"id":29795128606888,"position":1,"preview_image":{"aspect_ratio":1.0,"height":1299,"width":1299,"src":"\/\/admeshop.com\/cdn\/shop\/files\/InvitrometabolismNEG_c1fb323d-7298-4679-98cb-f3acae264649.png?v=1702464133"},"aspect_ratio":1.0,"height":1299,"media_type":"image","src":"\/\/admeshop.com\/cdn\/shop\/files\/InvitrometabolismNEG_c1fb323d-7298-4679-98cb-f3acae264649.png?v=1702464133","width":1299}],"requires_selling_plan":false,"selling_plan_groups":[],"content":"\u003cdiv id=\"formula-bar-name-box-wrapper\" class=\"name-box-enabled formula-bar-with-name-box-wrapper\" data-mce-fragment=\"1\"\u003e\n\u003cdiv id=\"formula-bar\" class=\"formula-bar formulabar-disabled\" data-mce-fragment=\"1\"\u003e\n\u003cdiv id=\"t-formula-bar-input-container\" data-mce-fragment=\"1\"\u003e\n\u003cdiv dir=\"ltr\" data-mce-fragment=\"1\"\u003e\n\u003cdiv spellcheck=\"false\" id=\"t-formula-bar-input\" data-mce-fragment=\"1\"\u003e\n\u003cdiv class=\"cell-input disabled-input\" role=\"combobox\" dir=\"ltr\" aria-autocomplete=\"list\" tabindex=\"0\" data-mce-fragment=\"1\" data-mce-tabindex=\"0\" contenteditable=\"false\" docs-unhandledkeys=\"\"\u003e\n\u003cspan data-mce-fragment=\"1\"\u003eThe non-CYP mediated metabolism of the compound is investigated using various recombinant enzymes and\/or human liver cytosol with enzyme-selective inhibitors. 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