Literature DB >> 29656650

Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain.

Robert P Law1, Stephen J Atkinson, Paul Bamborough, Chun-Wa Chung, Emmanuel H Demont, Laurie J Gordon, Matthew Lindon, Rab K Prinjha, Allan J B Watson1, David J Hirst.   

Abstract

The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but few reported inhibitors show selectivity within the BET family. Inhibitors with selectivity for the first or second bromodomain are desired to aid investigation of the biological function of these domains. Focused library screening identified a series of tetrahydroquinoxalines with selectivity for the second bromodomains of the BET family (BD2). Structure-guided optimization of the template improved potency, selectivity, and physicochemical properties, culminating in potent BET inhibitors with BD2 selectivity.

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Year:  2018        PMID： 29656650     DOI： 10.1021/acs.jmedchem.7b01666

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  6 in total

1.  Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.

Authors:  Pan Tang; Jifa Zhang; Jie Liu; Cheng-Ming Chiang; Liang Ouyang
Journal:  J Med Chem       Date:  2021-02-22       Impact factor: 7.446

Review 2.  Update on Novel Hormonal and Nonhormonal Male Contraceptive Development.

Authors:  Jill E Long; Min S Lee; Diana L Blithe
Journal:  J Clin Endocrinol Metab       Date:  2021-05-13       Impact factor: 5.958

3.  Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines.

Authors:  Hannah E Askey; James D Grayson; Joshua D Tibbetts; Jacob C Turner-Dore; Jake M Holmes; Gabriele Kociok-Kohn; Gail L Wrigley; Alexander J Cresswell
Journal:  J Am Chem Soc       Date:  2021-09-20       Impact factor: 15.419

Review 4.  Targeting bromodomain and extra-terminal proteins to inhibit neuroblastoma tumorigenesis through regulating MYCN.

Authors:  Xiyao Shi; Ying Wang; Longhui Zhang; Wenjie Zhao; Xiangpeng Dai; Yong-Guang Yang; Xiaoling Zhang
Journal:  Front Cell Dev Biol       Date:  2022-09-16

5.  Bromodomain-Selective BET Inhibitors Are Potent Antitumor Agents against MYC-Driven Pediatric Cancer.

Authors:  P Jake Slavish; Liying Chi; Mi-Kyung Yun; Lyudmila Tsurkan; Nancy E Martinez; Barbara Jonchere; Sergio C Chai; Michele Connelly; M Brett Waddell; Sourav Das; Geoffrey Neale; Zhenmei Li; William R Shadrick; Rachelle R Olsen; Kevin W Freeman; Jonathan A Low; Jeanine E Price; Brandon M Young; Nagakumar Bharatham; Vincent A Boyd; Jun Yang; Richard E Lee; Marie Morfouace; Martine F Roussel; Taosheng Chen; Daniel Savic; R Kiplin Guy; Stephen W White; Anang A Shelat; Philip M Potter
Journal:  Cancer Res       Date:  2020-07-10       Impact factor: 12.701

6.  Cyclic peptides can engage a single binding pocket through highly divergent modes.

Authors:  Karishma Patel; Louise J Walport; James L Walshe; Paul D Solomon; Jason K K Low; Daniel H Tran; Kevork S Mouradian; Ana P G Silva; Lorna Wilkinson-White; Alexander Norman; Charlotte Franck; Jacqueline M Matthews; J Mitchell Guss; Richard J Payne; Toby Passioura; Hiroaki Suga; Joel P Mackay
Journal:  Proc Natl Acad Sci U S A       Date:  2020-10-12       Impact factor: 12.779
  6 in total

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