The Design and Synthesis of a Highly Selective and In Vivo Capable Inhibitor of the Second Bromodomain (BD2) of the Bromodomain and Extra Terminal Domain (BET) Family of Proteins

Journal of Medicinal Chemistry
Alex PrestonEmmanuel H Demont

Abstract

Pan-BET inhibitors interact equipotently with the eight bromodomains of the BET family of proteins and have shown profound efficacy in a number of in vitro phenotypic assays and in vivo pre-clinical models in inflammation or oncology. A number of these inhibitors have progressed to the clinic where pharmacology-driven adverse events have been reported. To better understand the contribution of each domain to their efficacy and to improve from their safety profile, selective inhibitors are required. This article discloses the profile of GSK046, also known as iBET-BD2, a highly selective inhibitor of the second bromodomains of the BET proteins that has undergone extensive pre-clinical in vitro and in vivo characterisation.

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Citations

Nov 8, 2020·European Journal of Medicinal Chemistry·Tingting LiuJifu Hao
Feb 19, 2021·Journal of Medicinal Chemistry·Yi ZhangYuanxiang Wang
Apr 15, 2021·Current Opinion in Chemical Biology·Isabelle A EngelbergStephen V Frye
May 28, 2021·Journal of Medicinal Chemistry·Adam I Green, George M Burslem
Jul 13, 2021·Journal of Medicinal Chemistry·Francesco RianjongdeeEmmanuel H Demont
Oct 23, 2020·Journal of Medicinal Chemistry·Stuart J ConwayShaomeng Wang
Jul 22, 2020·Journal of Medicinal Chemistry·Robert J WatsonEmmanuel H Demont
Aug 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Qianqian WangXiaojun Yao

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