BCL2Hemmer

BCL2Hemmer, commonly referred to in English as BCL-2 inhibitors, denotes a class of small-molecule drugs that antagonize anti-apoptotic proteins of the BCL-2 family. They are a subset of BH3 mimetics designed to promote apoptosis in cancer cells by disabling survival signals provided by BCL-2–family proteins.

Mechanism of action involves binding to anti-apoptotic members such as BCL-2, BCL-XL, or BCL-w, thereby releasing pro-apoptotic proteins like BIM, BAX, and BAK. This unleashes the intrinsic mitochondrial pathway of apoptosis, leading to cytochrome c release and caspase activation. The degree of selectivity among BCL-2 family members influences both therapeutic effect and toxicity, with some inhibitors preferentially targeting BCL-2 and sparing BCL-XL to reduce platelet toxicity.

clinically used agents include venetoclax, the prototype BCL-2–selective inhibitor, and broader inhibitors such as navitoclax that also target BCL-XL. Venetoclax has been approved for various hematologic malignancies, including chronic lymphocytic leukemia and small lymphocytic lymphoma, and in combination regimens for acute myeloid leukemia in adults. Research continues across other lymphoid and myeloid diseases, often in combination with anti-CD20 antibodies, hypomethylating agents, or chemotherapy.

Safety considerations center on cytopenias and tumor lysis syndrome, particularly during dose ramp-up. Resistance can emerge through upregulation of alternative survival pathways (e.g., BCL-XL or MCL-1) or BCL2 mutations. As a therapeutic class, BCL2Hemmer remains an active area of oncology research, with ongoing efforts to improve selectivity, mitigate toxicity, and overcome resistance.