6vuj
From Proteopedia
Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 15c (N,N-diethyl-3',4'-dimethoxy-6-(1-methyl-5-oxopyrrolidin-3-yl)-[1,1'-biphenyl]-3-sulfonamide)
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 PubMedN-Methylpyrrolidone is one of several chemotypes that have been described as a mimetic of acetyl-lysine in the development of bromodomain inhibitors. In this paper, we describe the synthesis of a 4-phenyl substituted analogue - 1-methyl-4-phenylpyrrolidin-2-one - and the use of aryl substitution reactions as a divergent route for derivatives. Ultimately, this has led to structurally complex, chiral compounds with progressively improved affinity as inhibitors of bromodomain-containing protein 4. Substituted 1-methyl-4-phenylpyrrolidin-2-ones - Fragment-based design of N-methylpyrrolidone-derived bromodomain inhibitors.,Hilton-Proctor JP, Ilyichova O, Zheng Z, Jennings IG, Johnstone RW, Shortt J, Mountford SJ, Scanlon MJ, Thompson PE Eur J Med Chem. 2020 Apr 1;191:112120. doi: 10.1016/j.ejmech.2020.112120. Epub, 2020 Feb 12. PMID:32120339[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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