Allosteric modulators of MEK1: drug design and discovery

J Shang, S Lu, Y Jiang, J Zhang - Chemical Biology & Drug …, 2016 - Wiley Online Library
J Shang, S Lu, Y Jiang, J Zhang
Chemical Biology & Drug Design, 2016Wiley Online Library
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 …
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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