Selective inhibitors of human mPGES-1 from structure-based computational screening
Selective inhibitors of human mPGES-1 from structure-based computational screening
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DOI：
10.1016/j.bmcl.2017.06.075
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发表时间：
2017-08-15
影响因子：
2.7
通讯作者：
Zhan, Chang-Guo
中科院分区：
文献类型：
--
作者：
Zhou, Ziyuan;Yuan, Yaxia;Zhan, Chang-Guo
人mPGES-1被认为是下一代抗炎药物的有前途的靶点。尽管文献中已报道了各种mPGES-1抑制剂，但很少有进入临床试验，迄今为止还没有一种被证明具有临床用途。为了开发下一代炎症相关疾病的治疗药物，非常希望设计和发现具有新支架的mPGES-1的新抑制剂。在这里，我们报告了一系列新的，有效的和选择性的人mPGES-1抑制剂与不同的支架，通过结合计算和实验研究的鉴定。这些新的mPGES-1抑制剂的结合结构的计算建模提供了一些有趣的线索，合理设计的抑制剂的改性结构，更有利地结合mPGES-1。(C)2017爱思唯尔有限公司版权所有
Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs. Although various mPGES-1 inhibitors have been reported in literature, few have entered clinical trials and none has been proven clinically useful so far. It is highly desired for developing the next generation of therapeutics for inflammation-related diseases to design and discover novel inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a series of new, potent and selective inhibitors of human mPGES-1 with diverse scaffolds through combined computational and experimental studies. The computationally modeled binding structures of these new inhibitors of mPGES-1 provide some interesting clues for rational design of modified structures of the inhibitors to more favorably bind with mPGES-1. (C) 2017 Elsevier Ltd. All rights reserved.