Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins - PubMed (original) (raw)

. 2006 Oct 19;49(21):6139-42.

doi: 10.1021/jm060460o.

Zaneta Nikolovska-Coleska, Chao-Yie Yang, Renxiao Wang, Guozhi Tang, Jie Guo, Sanjeev Shangary, Su Qiu, Wei Gao, Dajun Yang, Jennifer Meagher, Jeanne Stuckey, Krzysztof Krajewski, Sheng Jiang, Peter P Roller, Hatice Ozel Abaan, York Tomita, Shaomeng Wang

Affiliations

• PMID: 17034116
• DOI: 10.1021/jm060460o

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

Guoping Wang et al. J Med Chem. 2006.

Abstract

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 Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC(50) value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

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