体内
化学
Bcl xL型
IC50型
癌症研究
细胞生长
细胞培养
结构-活动关系
药理学
体外
立体化学
程序性细胞死亡
细胞凋亡
生物化学
生物
生物技术
遗传学
作者
Angelo Aguilar,Haibin Zhou,Jianfang Chen,Liu Liu,Longchuan Bai,Donna McEachern,Chao Yang,Jennifer L. Meagher,Jeanne A. Stuckey,Shaomeng Wang
摘要
Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K(i) values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.
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