Literature DB >> 26230603

Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors.

Paul Bamborough, Chun-wa Chung, Rebecca C Furze, Paola Grandi1, Anne-Marie Michon1, Robert J Sheppard, Heather Barnett, Hawa Diallo, David P Dixon, Clement Douault, Emma J Jones, Bhumika Karamshi, Darren J Mitchell, Rab K Prinjha, Christina Rau1, Robert J Watson, Thilo Werner1, Emmanuel H Demont.   

Abstract

ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.

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Year:  2015        PMID： 26230603     DOI： 10.1021/acs.jmedchem.5b00773

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


  23 in total

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Authors:  Eric S Manas; Darren V S Green
Journal:  J Comput Aided Mol Des       Date:  2017-01-09       Impact factor: 3.686

Review 2.  Biological function and histone recognition of family IV bromodomain-containing proteins.

Authors:  Jonathan T Lloyd; Karen C Glass
Journal:  J Cell Physiol       Date:  2017-06-13       Impact factor: 6.384

3.  Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain.

Authors:  Jamie C Gay; Brian E Eckenroth; Chiara M Evans; Cassiano Langini; Samuel Carlson; Jonathan T Lloyd; Amedeo Caflisch; Karen C Glass
Journal:  Proteins       Date:  2018-12-27

Review 4.  Structural features and inhibitors of bromodomains.

Authors:  Jamel Meslamani; Steven G Smith; Roberto Sanchez; Ming-Ming Zhou
Journal:  Drug Discov Today Technol       Date:  2016-09-22

5.  The ATAD2 bromodomain binds different acetylation marks on the histone H4 in similar fuzzy complexes.

Authors:  Cassiano Langini; Amedeo Caflisch; Andreas Vitalis
Journal:  J Biol Chem       Date:  2017-08-10       Impact factor: 5.157

6.  Optimization of Naphthyridones into Selective TATA-Binding Protein Associated Factor 1 (TAF1) Bromodomain Inhibitors.

Authors:  Michael A Clegg; Natalie H Theodoulou; Paul Bamborough; Chun-Wa Chung; Peter D Craggs; Emmanuel H Demont; Laurie J Gordon; Gemma M Liwicki; Alex Phillipou; Nicholas C O Tomkinson; Rab K Prinjha; Philip G Humphreys
Journal:  ACS Med Chem Lett       Date:  2021-08-03       Impact factor: 4.632

7.  Structural Insights into the Recognition of Mono- and Diacetylated Histones by the ATAD2B Bromodomain.

Authors:  Jonathan T Lloyd; Kyle McLaughlin; Mulu Y Lubula; Jamie C Gay; Andrea Dest; Cong Gao; Margaret Phillips; Marco Tonelli; Gabriel Cornilescu; Matthew R Marunde; Chiara M Evans; Samuel P Boyson; Samuel Carlson; Michael-Christopher Keogh; John L Markley; Seth Frietze; Karen C Glass
Journal:  J Med Chem       Date:  2020-10-21       Impact factor: 7.446

Review 8.  Epigenomic regulation of oncogenesis by chromatin remodeling.

Authors:  R Kumar; D-Q Li; S Müller; S Knapp
Journal:  Oncogene       Date:  2016-01-25       Impact factor: 9.867

9.  A Chemical Probe for the ATAD2 Bromodomain.

Authors:  Paul Bamborough; Chun-Wa Chung; Emmanuel H Demont; Rebecca C Furze; Andrew J Bannister; Ka Hing Che; Hawa Diallo; Clement Douault; Paola Grandi; Tony Kouzarides; Anne-Marie Michon; Darren J Mitchell; Rab K Prinjha; Christina Rau; Samuel Robson; Robert J Sheppard; Richard Upton; Robert J Watson
Journal:  Angew Chem Int Ed Engl       Date:  2016-08-17       Impact factor: 15.336

Review 10.  AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors.

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Journal:  Eur J Med Chem       Date:  2021-04-10       Impact factor: 7.088
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