Structure-based Design of Flavonoid Compounds As a New Class of Small-molecule Inhibitors of the Anti-apoptotic Bcl-2 Proteins

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2007 Jun 8

PMID 17552510

Citations 11

Authors

Guozhi Tang

Ke Ding

Zaneta Nikolovska-Coleska

Chao-Yie Yang

Su Qiu

Sanjeev Shangary

Renxiao Wang

Jie Guo

Wei Gao

Jennifer Meagher

Jeanne Stuckey

Krzysztof Krajewski

Sheng Jiang

Peter P Roller

Shaomeng Wang

Affiliations

Soon will be listed here.

Abstract

Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-231 breast cancer cell line with an IC50 value of 110 nM and effectively induces apoptosis.

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