| Structural highlights
Function
[BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.[1]
Publication Abstract from PubMed
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.
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.,Preston A, Atkinson SJ, Bamborough P, Chung CW, Craggs PD, Gordon LJ, Grandi P, Gray J, Jones EJ, Lindon M, Michon AM, Mitchell DJ, Prinjha RK, Rianjongdee F, Rioja I, Seal J, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH J Med Chem. 2020 Jul 21. doi: 10.1021/acs.jmedchem.0c00605. PMID:32691591[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ LeRoy G, Rickards B, Flint SJ. The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell. 2008 Apr 11;30(1):51-60. doi: 10.1016/j.molcel.2008.01.018. PMID:18406326 doi:10.1016/j.molcel.2008.01.018
- ↑ Preston A, Atkinson SJ, Bamborough P, Chung CW, Craggs PD, Gordon LJ, Grandi P, Gray J, Jones EJ, Lindon M, Michon AM, Mitchell DJ, Prinjha RK, Rianjongdee F, Rioja I, Seal J, Taylor S, Wall ID, Watson RJ, Woolven JM, Demont EH. 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. J Med Chem. 2020 Jul 21. doi: 10.1021/acs.jmedchem.0c00605. PMID:32691591 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c00605
|
