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Allosteric modulators of MEK1: drug design and discovery
Author(s) -
Shang Jialin,
Lu Shaoyong,
Jiang Yongjun,
Zhang Jian
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12780
Subject(s) - allosteric regulation , mapk/erk pathway , drug discovery , signal transduction , protein kinase a , kinase , chemistry , microbiology and biotechnology , cancer research , biology , enzyme , biochemistry
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.