Structure-based design of flavonoid compounds as a new class of small-molecule inhibitors of the anti-apoptotic Bcl-2 proteins

  • J Med Chem. 2007 Jul 12;50(14):3163-6. doi: 10.1021/jm070383c.
Guozhi Tang  1 ,  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
  • 1. Comprehensive Cancer Center and Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
PMID: 17552510 DOI: 10.1021/jm070383c
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.