摘要
The anti-apoptotic Bcl-2 proteins are attractive targets for anti-cancer drug development, and the discovery of their selective inhibitors has become a research focus. In this Letter, obvious differences in the P1 pocket of the active site between Bcl-2, Bcl-x(L), and Mc1-1 proteins were proposed by the structural comparison of these proteins. As a result, the groups in their inhibitors binding to the P1 pockets may have significant effect on the selectivity for these proteins. Based on this hypothesis, five types of derivatives of the lead compound B-1 were designed, and several highly selective inhibitors of Bcl-x(L) (E-1) or Mcl-1 proteins (G) were found. The selective inhibitors of Mc1-1 protein found in this Letter provide new structural types for the development of novel antitumor agents.
- 出版日期2016-11-1
- 单位中国人民解放军第二军医大学; 上海医药工业研究院; 中国药科大学