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
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DOI：
10.1021/jm070383c
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发表时间：
2007-07-12
影响因子：
7.3
通讯作者：
Wang, Shaomeng
中科院分区：
文献类型：
--
作者：
Tang, Guozhi;Ding, Ke;Wang, Shaomeng
采用基于结构的策略设计类黄酮化合物来模拟Bim BH3肽，作为一类新的抗凋亡Bcl-2蛋白抑制剂。最有效的化合物4 （BI-33）与Bcl-2和Mcl-1结合，K-i值分别为17和18 nM。化合物4抑制MDA-MB-231乳腺癌细胞株细胞生长，IC50值为110 nM，并有效诱导细胞凋亡。
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 K-i 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.