Allosteric modulators of MEK1: drug design and discovery
Allosteric modulators of MEK1: drug design and discovery
复制标题
DOI：
10.1111/cbdd.12780
复制
发表时间：
2016-10
影响因子：
3
通讯作者：
Jialin Shang;Shaoyong Lu;Yong-Jun Jiang;Jian Zhang
中科院分区：
文献类型：
--
作者：
Jialin Shang;Shaoyong Lu;Yong-Jun Jiang;Jian Zhang
丝裂原活化蛋白激酶激酶（MAPKK，MEK）介导信号转导，控制细胞增殖和存活。MEK在Ras-Raf-MEK-ERK信号通路中占据关键下游位置，这意味着抑制MEK将有效抑制肿瘤细胞生长，在癌症治疗中具有潜在应用。基于MEK调节剂的有希望的治疗效果，已经在这类中进行了持续的努力。本文综述了MEK 1变构调节剂的发现和发展，并将其分为四类。本文还综述了这些调节剂的变构作用机制和最新的临床研究进展。
Mitogen‐activated protein kinase kinase (MAPKK, MEK) mediates signal transduction, controlling cell proliferation and survival. MEK occupies a key downstream position in the Ras‐Raf‐MEK‐ERK signaling pathway, implying that inhibition of MEK will potently suppress tumor cell growth, with potential applications in cancer therapy. Based on the promising therapeutic effects of MEK modulators, continued efforts have been made in this class. Here, we review the discovery and development of MEK1 allosteric modulators, classifying them into four structural groups. The allosteric mechanisms and recent clinical progress involving these modulators are also reviewed.