Structure-based Design of Potent Small-molecule Inhibitors of Anti-apoptotic Bcl-2 Proteins

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2006 Oct 13

PMID 17034116

Citations 121

Authors

Guoping Wang

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

Soon will be listed here.

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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