{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["He Y"],"funding":["Deutsche Forschungsgemeinschaft","NCI NIH HHS","National Institutes of Health","NIH HHS","Leukemia and Lymphoma Society"],"pagination":["95"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7364785"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["<h4>Background</h4>Patients with advanced T cell lymphomas (TCLs) have limited therapeutic options and poor outcomes in part because their TCLs evade apoptosis through upregulation of anti-apoptotic Bcl-2 proteins. Subsets of TCL cell lines, patient-derived xenografts (PDXs), and primary patient samples depend on Bcl-xL for survival. However, small molecule Bcl-xL inhibitors such as ABT263 have failed during clinical development due to on-target and dose-limiting thrombocytopenia.<h4>Methods</h4>We have developed DT2216, a proteolysis targeting chimera (PROTAC) targeting Bcl-xL for degradation via Von Hippel-Lindau (VHL) E3 ligase, and shown that it has better anti-tumor activity but is less toxic to platelets compared to ABT263. Here, we examined the therapeutic potential of DT2216 for TC"],"journal":["Journal of hematology & oncology"],"pubmed_title":["DT2216-a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas."],"pmcid":["PMC7364785"],"funding_grant_id":["R01CA219836","R01 CA242003","R01CA241191","R35 CA231958","R35CA239158","R01 CA219836","#7011-16","R21CA223371","R01CA211963","R01 CA211963","R01CA242003","KO 4627/2-1"],"pubmed_authors":["Wiegand JS","Lv D","Ortiz YT","Weinstock DM","Zhang P","Li W","Thummuri D","He Y","Zhang X","Zhou D","Palmer AC","Budamagunta V","Zheng G","Koch R","Khan S"],"additional_accession":[]},"is_claimable":false,"name":"DT2216-a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas.","description":"<h4>Background</h4>Patients with advanced T cell lymphomas (TCLs) have limited therapeutic options and poor outcomes in part because their TCLs evade apoptosis through upregulation of anti-apoptotic Bcl-2 proteins. Subsets of TCL cell lines, patient-derived xenografts (PDXs), and primary patient samples depend on Bcl-xL for survival. However, small molecule Bcl-xL inhibitors such as ABT263 have failed during clinical development due to on-target and dose-limiting thrombocytopenia.<h4>Methods</h4>We have developed DT2216, a proteolysis targeting chimera (PROTAC) targeting Bcl-xL for degradation via Von Hippel-Lindau (VHL) E3 ligase, and shown that it has better anti-tumor activity but is less toxic to platelets compared to ABT263. Here, we examined the therapeutic potential of DT2216 for TC","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2025-04-04T20:16:52.465Z","creation":"2025-04-04T20:16:52.465Z"},"accession":"S-EPMC7364785","cross_references":{"pubmed":["32677976"],"doi":["10.1186/s13045-020-00928-9"]}}