Shang Jialin, Lu Shaoyong, Jiang Yongjun, Zhang Jian
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
School of Biotechnology and Chemical Engineering, Ningbo Institute of Technology, Zhejiang University, Ningbo, China.
Chem Biol Drug Des. 2016 Oct;88(4):485-97. doi: 10.1111/cbdd.12780. Epub 2016 Jun 1.
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.
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的下游位置，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价值。基于MEK调节剂有前景的治疗效果，该领域一直在持续努力。在此，我们综述MEK1变构调节剂的发现与开发，将它们分为四个结构组。还综述了涉及这些调节剂的变构机制和近期临床进展。
