Description
A Bcl2-BH4 domain antagonist (Ki = 3.3 nM); selective for Bcl-2 over Bcl-xL, Mcl-1, A1/Bfl-1, and Bcl-2 lacking the BH4 domain (Kis = >500, >500, >500, and 654.8 nM, respectively); binds to BH1-, BH2-, or BH3 domain-deficient Bcl-2 (Kis = 12.4, 7.6, and 23.4 nM, respectively); induces Bax activation in HT cells, which lack endogenous Bcl-2, and in HT cells overexpressing Bcl-2, indicating a context-specific Bcl-2-independent mechanism of cell death; is cytotoxic against a panel of NSCLC and SCLC cell lines (IC50s = 0.2-1.73 µM); reduces tumor growth and induces tumoral caspase-3 activation in an H460 lung cancer mouse xenograft model at 10, 20, and 30 mg/kg