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Chemical modulators for epigenome reader domains as emerging epigenetic therapies for cancer and inflammation.

ABSTRACT: Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic therapy with small molecules to modulate molecular interactions of epigenome reader domain proteins with PTMs. In addition to BET, the other emerging targets include non-BET acetyl-lysine and methyl-lysine reader domains. This review covers the key chemical modulators of the aforementioned epigenome reader proteins.

SUBMITTER: Zaware N

PROVIDER: S-EPMC5581715 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Chemical modulators for epigenome reader domains as emerging epigenetic therapies for cancer and inflammation.

Zaware Nilesh N Zhou Ming-Ming MM

Current opinion in chemical biology 20170706

Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic the ...[more]

PMID: 28689146

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