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Allosteric modulators of MEK1: drug design and discovery
Jialin Shang1, Shaoyong Lu1, Yongjun Jiang2
1Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Abstract:
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.
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