BDA-366

Bcl2-BH4结构域拮抗剂（Ki=3.3nM）；对Bcl-2具有选择性，优于Bcl-xL、Mcl-1、A1/Bfl-1和缺乏BH4结构域的Bcl-2（Kis分别为>500、>500、>500和654.8nM）；可与BH1-、BH2-或BH3结构域缺陷的Bcl-2结合（Kis分别为12.4、7.6和23.4nM）；在缺乏内源性Bcl-2的HT细胞和过表达Bcl-2的HT细胞中诱导Bax活化，表明存在一种特定于环境的Bcl-2独立的细胞死亡机制；对一组NSCLC和SCLC细胞系有细胞毒性（IC50s=0.2-1.73µM）；10、20和30mg/kg剂量可降低H460肺癌小鼠异种移植模型中的肿瘤生长并诱导肿瘤caspase-3活化。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.分子式C24H29N3O4分子量423.5CCN(CC)C[C@@H](O)CNC(C=C1)=C(C(C2=CC=CC=C2C3=O)=O)C3=C1NC[C@H]4CO4