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

详细信息    查看全文

• 作者：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. R
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：July 12, 2007
• 年：2007
• 卷：50
• 期：14
• 页码：3163 - 3166
• 全文大小：311K
• 年卷期：v.50,no.14(July 12, 2007)
• ISSN：1520-4804

文摘

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