Allosteric modulators of MEK1: drug design and discovery

作者：Shang, Jialin; Lu, Shaoyong; Jiang, Yongjun; Zhang, Jian^*

来源：Chemical Biology & Drug Design, 2016, 88(4): 485-497.

DOI：10.1111/cbdd.12780

• allosteric mechanism
• allosteric modulators
• cancer treatment
• MEK1
• signaling pathway

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.

• 出版日期2016-10
• 单位上海交通大学; 浙江大学宁波理工学院; 浙江大学