Discovery of Epigenetic Regulator
I‑BET762:
Lead Optimization to Afford a Clinical Candidate Inhibitor of the
BET Bromodomains

Alain Daugan (1438681); Andrea C. Haynes (1899865); Antonia Lewis (1899874); Catherine
A. Clément (1899847); Chun-wa Chung (1343454); Edwige Nicodème (1738171); Iain J. Uings (1899871); Jacqueline E. Mordaunt (1899853); Jason Witherington (1399264); Jean-Marie Brusq (1804576); Jérôme Toum (1738159); Leanne Cutler (1738141); Mélanie Barnathan (1899844); Miriam Crowe (1899868); Myriam Ajakane (1438696); Nicholas N. Smithers (1899850); Nigel Parr (449756); Olivier Mirguet (1738153); Olivier Pineau (1899862); Paul Bamborough (1343466); Phillip Jeffrey (1899859); Rab K. Prinjha (449759); Richard M. Grimes (1899856); Romain Gosmini (1738168)

Discovery of Epigenetic Regulator I‑BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

Abstract

The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure–activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers

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Last time updated on 12/02/2018