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小分子溴结构域抑制剂的临床进展与药理学

Clinical progress and pharmacology of small molecule bromodomain inhibitors.

作者信息

Theodoulou Natalie H, Tomkinson Nicholas Co, Prinjha Rab K, Humphreys Philip G

机构信息

Epinova Epigenetics Discovery Performance Unit, GlaxoSmithKline R&D, Stevenage, Hertfordshire SG1 2NY, UK; WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.

WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.

出版信息

Curr Opin Chem Biol. 2016 Aug;33:58-66. doi: 10.1016/j.cbpa.2016.05.028. Epub 2016 Jun 10.

Abstract

Bromodomains have emerged as an exciting target class for drug discovery over the past decade. Research has primarily focused on the bromodomain and extra terminal (BET) family of bromodomains, which has led to the development of multiple small molecule inhibitors and an increasing number of clinical assets. The excitement centred on the clinical potential of BET inhibition has stimulated intense interest in the broader family and the growing number of non-BET bromodomain chemical probes has facilitated phenotypic investigations, implicating these targets in a variety of disease pathways including cancer, inflammation, embryonic development and neurological disorders.

摘要

在过去十年中,溴结构域已成为药物研发中一个令人兴奋的靶点类别。研究主要集中在溴结构域和额外末端(BET)家族的溴结构域上,这已导致多种小分子抑制剂的开发以及越来越多的临床资产。围绕BET抑制的临床潜力所产生的兴奋之情激发了对更广泛家族的浓厚兴趣,并且越来越多的非BET溴结构域化学探针促进了表型研究,表明这些靶点涉及包括癌症、炎症、胚胎发育和神经疾病在内的多种疾病途径。

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