8pxn
From Proteopedia
N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH (1R,1'R)-7,7'-(ethane-1,2-diylbis(oxy))bis(1,3-dimethyl-1,3-dihydro-2H-benzo[d]azepin-2-one)
Structural highlights
DiseaseBRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.[1] [2] FunctionBRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedThe 1,3-dihydro-2H-benzo[d]azepin-2-ones are potent and ligand-efficient pan-BET bromodomain inhibitors. Here we describe the extension of this template to exploit a bivalent mode of action, binding simultaneously to both bromodomains. Initially the linker length and attachment vectors compatible with bivalent binding were explored, leading to the discovery of exceptionally potent bivalent BET inhibitors within druglike rule-of-5 space. Design and Characterization of 1,3-Dihydro-2H-benzo[d]azepin-2-ones as Rule-of-5 Compliant Bivalent BET Inhibitors.,Bamborough P, Chung CW, Goodwin NC, Mitchell DJ, Neipp CE, Phillipou A, Preston A, Prinjha RK, Soden PE, Watson RJ, Demont EH ACS Med Chem Lett. 2023 Aug 14;14(9):1231-1236. doi: , 10.1021/acsmedchemlett.3c00242. eCollection 2023 Sep 14. PMID:37736196[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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