title: Privileged diazepine compounds and their emergence as bromodomain inhibitors.
abstract: Chemical compounds built on a diazepine scaffold have recently emerged as potent inhibitors of the acetyl-lysine binding activity of bromodomain-containing proteins, which is required for gene transcriptional activation in cancer and inflammation. Not only have these chemical compounds validated bromodomains as attractive epigenetic drug targets, but they have also brought to the forefront another application of the diazepine, which had already been regarded as a versatile chemical scaffold in rational drug design. This article reviews the success of diazepine compounds as therapeutic agents and examines the unique chemical and geometric features of this privileged scaffold that make it an excellent template for developing potent and selective molecules that control bromodomain-related gene expression in human diseases.
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sanchez
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA. Electronic address: ming-ming.zhou@mssm.edu.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects
chemical_list: D001381:Azepines; D009687:Nuclear Proteins
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