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"https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F115797116%2FIAP_antagonist_GDC_0917_is_more_potent_than_Debio1143_in_promoting_cell_death_c_IAP1_degradation_and_tumor_growth_inhibition%3Fshow_translation%3Dtrue"; window.loswp.previewableAttachments = [{"id":112103578,"identifier":"Attachment_112103578","shouldShowBulkDownload":false}]; window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":115797116,"created_at":"2024-03-04T19:10:33.854-08:00","from_world_paper_id":250904567,"updated_at":"2025-01-10T19:33:47.036-08:00","_data":{"publisher":"Springer Science and Business Media LLC","ai_abstract":"Proper regulation of cell death and survival is essential for cellular homeostasis. Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking cell death, modulating signal transduction, and affecting cellular proliferation. By contributing to the evasion of cell death, IAP proteins enhance the resistance of cancer cells to treatment with antitumor agents and impact tumor progression. IAP antagonism results in the activation of noncanonical NF-kB signaling and TNF-mediated cell death. A number of IAP antagonists have been tested in clinic with overall favorable pharmacological properties, for example, GDC-0917 and Debio1143. Here, we compare the cell death-inducing and anti-tumor capabilities of GDC-0917 and Debio1143, and investigate their tumor and plasma concentrations in two preclinical mouse tumor models. We find that GDC-0917 is more potent in cells and in vivo compared to Debio1143 and could not verify the tumor-selective tissue distribution previously reported. Thus, we conclude that c-IAP1 degradation and cell death induction are better predictors of the potential application of IAP antagonists in the clinical setting than tumor to plasma exposure ratios.","publication_name":"Cell Death \u0026amp; Disease"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [33147969]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card ds-work-card--no-bottom-spacing"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":112103578,"attachmentType":"pdf"}"><img alt="First page of “IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/112103578/mini_magick20240305-1-oxlail.png?1709608282" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="33147969" href="https://independent.academia.edu/DomagojVucic"><img alt="Profile image of Domagoj Vucic" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Domagoj Vucic</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">Cell Death &amp; Disease</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">3 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 115797116; const worksViewsPath = "/v0/works/views?subdomain_param=api&work_ids%5B%5D=115797116"; const getWorkViews = async (workId) => { const response = await fetch(worksViewsPath); if (!response.ok) { throw new Error('Failed to load work views'); } const data = await response.json(); return data.views[workId]; }; // Get the view count for the work - we send this immediately rather than waiting for // the DOM to load, so it can be available as soon as possible (but without holding up // the backend or other resource requests, because it's a bit expensive and not critical). const viewCount = await getWorkViews(workId); 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} })();</script></div><p class="ds-work-card--detail ds2-5-body-md">AI-generated Abstract</p><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Proper regulation of cell death and survival is essential for cellular homeostasis. Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking cell death, modulating signal transduction, and affecting cellular proliferation. By contributing to the evasion of cell death, IAP proteins enhance the resistance of cancer cells to treatment with antitumor agents and impact tumor progression. IAP antagonism results in the activation of noncanonical NF-kB signaling and TNF-mediated cell death. A number of IAP antagonists have been tested in clinic with overall favorable pharmacological properties, for example, GDC-0917 and Debio1143. Here, we compare the cell death-inducing and anti-tumor capabilities of GDC-0917 and Debio1143, and investigate their tumor and plasma concentrations in two preclinical mouse tumor models. We find that GDC-0917 is more potent in cells and in vivo compared to Debio1143 and could not verify the tumor-selective tissue distribution previously reported. 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="48404618" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/48404618/Antagonism_of_c_IAP_and_XIAP_Proteins_Is_Required_for_Efficient_Induction_of_Cell_Death_by_Small_Molecule_IAP_Antagonists">Antagonism of c-IAP and XIAP Proteins Is Required for Efficient Induction of Cell Death by Small-Molecule IAP Antagonists</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33147969" href="https://independent.academia.edu/DomagojVucic">Domagoj Vucic</a></div><p class="ds-related-work--metadata ds2-5-body-xs">ACS Chemical Biology, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)","attachmentId":88226168,"attachmentType":"pdf","work_url":"https://www.academia.edu/82550016/Overcoming_chemotherapy_drug_resistance_by_targeting_inhibitors_of_apoptosis_proteins_IAPs_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/82550016/Overcoming_chemotherapy_drug_resistance_by_targeting_inhibitors_of_apoptosis_proteins_IAPs_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container 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href="https://www.academia.edu/12014627/Potent_and_Selective_Small_Molecule_Inhibitors_of_cIAP1_2_Proteins_Reveal_That_the_Binding_of_Smac_Mimetics_to_XIAP_BIR3_Is_Not_Required_for_Their_Effective_Induction_of_Cell_Death_in_Tumor_Cells">Potent and Selective Small-Molecule Inhibitors of cIAP1/2 Proteins Reveal That the Binding of Smac Mimetics to XIAP BIR3 Is Not Required for Their Effective Induction of Cell Death in Tumor Cells</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="29913514" href="https://independent.academia.edu/ChaoyieYang">Chao-yie Yang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">ACS Chemical Biology, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Potent and Selective Small-Molecule Inhibitors of cIAP1/2 Proteins Reveal 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href="https://www.academia.edu/15371015/The_inhibitors_of_apoptosis_IAPs_and_their_emerging_role_in_cancer">The inhibitors of apoptosis (IAPs) and their emerging role in cancer</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34521873" href="https://uottawa.academia.edu/RobertKorneluk">Robert Korneluk</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34574296" href="https://independent.academia.edu/StephenBaird2">Stephen Baird</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Oncogene, 1999</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The inhibitors of apoptosis (IAPs) and their emerging role in 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class="ds-related-work--metadata ds2-5-body-xs">Oncogene, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"IAP-targeted therapies for cancer","attachmentId":43207644,"attachmentType":"pdf","work_url":"https://www.academia.edu/15430594/IAP_targeted_therapies_for_cancer","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/15430594/IAP_targeted_therapies_for_cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="15" data-entity-id="81429267" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/81429267/Dimeric_Macrocyclic_Antagonists_of_IAP_Proteins_for_the_Treatment_of_Cancer">Dimeric Macrocyclic Antagonists of IAP Proteins for the Treatment of Cancer</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="62994445" href="https://independent.academia.edu/CChaudhry">Charu Chaudhry</a></div><p class="ds-related-work--metadata ds2-5-body-xs">ACS Medicinal Chemistry Letters, 2015</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Dimeric Macrocyclic Antagonists of IAP Proteins for the Treatment of 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