Allosteric modulators of MEK1: drug design and discovery. (1st June 2016)

• Record Type: Journal Article
• Authors: Shang, Jialin; Lu, Shaoyong; Jiang, Yongjun; Zhang, Jian
• Is Part Of: Chemical biology & drug design. Volume 88:Number 4(2016)
• Page Start: 485
• Page End: 497
• Publication Date: 2016-06-01
• Subjects: allosteric mechanism -- allosteric modulators -- cancer treatment -- MEK1 -- signaling pathway; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12780
• Languages: English
• ISSNs: 1747-0277

Abstract

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. Abstract : MEK1 allosteric modulators show high anticancer efficacy. We classify four groups of MEK1 modulators by structure. Significant cocrystal structures, current preclinical, and clinical results involving cotherapies are also discussed.