{"entity":{"id":"bcl2-inhibitors","kind":"technology","name":"BCL-2 inhibitors","aka":[],"tldr":"Drugs that switch off BCL-2, the protein that lets cancer cells refuse to die; venetoclax transformed treatment of chronic lymphocytic leukaemia and acute myeloid leukaemia.","summary":"BCL-2 blocks the mitochondrial pathway of apoptosis. Venetoclax, a BH3 mimetic approved in 2016, produces deep remissions in chronic lymphocytic leukaemia in fixed-duration combinations with obinutuzumab or BTK inhibitors, and with azacitidine it became standard for older patients with acute myeloid leukaemia. Second-generation inhibitors such as sonrotoclax aim for greater selectivity, and BCL-XL and MCL-1 inhibitors target the related proteins that mediate resistance.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Venetoclax","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Venetoclax"}],"tags":[],"related":[],"cancers":["cll","aml"],"sections":["targeted-therapy"],"technologies":[],"targets":["bcl2"],"drugs":["venetoclax","sonrotoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Small molecules mimic BH3-only proteins, binding BCL-2's groove so that BAX and BAK are released to trigger mitochondrial apoptosis.","strengths":["Deep, durable responses and fixed-duration treatment in CLL","Standard of care in unfit AML","Oral"],"limitations":["Tumour lysis syndrome requires ramp-up","Neutropenia","Resistance through 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