Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins

A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a K-i value of 290 nM and also to BclxL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner.