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

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

Affiliation

  • 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.

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