3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1. [Research Support, Non-U.S. Gov't] | |
Song, T.; Li, X.; Chang, X.; Liang, X.; Zhao, Y.; Wu, G.; . . . Zhang, Z. | |
2013 | |
发表期刊 | Bioorg Med Chem |
卷号 | 21期号:1页码:11-20 |
摘要 | Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1), a library of 9-substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure–activity relationship study, and site-directed mutation, compound 6d (3-(4-aminophenylthio)-8-oxo-8Hacenaphtho[1,2-b]pyrrole-9-3-phenyl)propylamine) was identified to span p2–p4 pockets of Mcl-1, Bcl-2 and Bcl-xL, and then exhibited 9- to 35-fold better affinity to the three targets than 3 (IC50 = 10, 20 and 18 nM, respectively), which led to greater activity in induction of apoptosis in multiple cancer cell lines. Different contribution of p4 pocket to binding Bcl-2 and Mcl-1 was also investigated by plotting the potency and the HAC of the derivatives. |
学科领域 | 代谢物组学 |
收录类别 | SCI |
语种 | 英语 |
文献类型 | 期刊论文 |
条目标识符 | http://ir.qibebt.ac.cn/handle/337004/1552 |
专题 | 代谢物组学研究组 |
推荐引用方式 GB/T 7714 | Song, T.,Li, X.,Chang, X.,et al. 3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1. [Research Support, Non-U.S. Gov't][J]. Bioorg Med Chem,2013,21(1):11-20. |
APA | Song, T..,Li, X..,Chang, X..,Liang, X..,Zhao, Y..,...&. . . Zhang, Z..(2013).3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1. [Research Support, Non-U.S. Gov't].Bioorg Med Chem,21(1),11-20. |
MLA | Song, T.,et al."3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1. [Research Support, Non-U.S. Gov't]".Bioorg Med Chem 21.1(2013):11-20. |
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