FCN-683

FCN-683 is a second-generation, highly selective, oral small molecule inhibitor of B-cell lymphoma 2 (BCL-2). Developed by Fochon Biosciences (a subsidiary of Fosun Pharma), it is designed to overcome resistance to first-generation BCL-2 inhibitors like venetoclax. FCN-683 demonstrates sub-nanomolar affinity for both wild-type BCL-2 and clinically relevant venetoclax-resistant mutants, including G101V, D103, and V156D. By selectively binding to the hydrophobic groove of BCL-2, it displaces pro-apoptotic proteins to induce apoptosis in B-cell malignancies. Its high selectivity for BCL-2 over BCL-xL potentially reduces the risk of thrombocytopenia. It is currently being evaluated in Phase 1 clinical trials for relapsed or refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML).