5hls
Crystal structure of the first bromodomain of human BRD4 bound to CPI-0610
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 PubMedIn recent years, inhibition of the interaction between the bromodomain and extra-terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease-relevant genes, including MYC, BCL-2, and NF-kappaB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET-dependent gene expression in vivo, demonstrates antitumor efficacy in an MV-4-11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI-0610). Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials.,Albrecht BK, Gehling VS, Hewitt MC, Vaswani RG, Cote A, Leblanc Y, Nasveschuk CG, Bellon S, Bergeron L, Campbell R, Cantone N, Cooper MR, Cummings RT, Jayaram H, Joshi S, Mertz JA, Neiss A, Normant E, O'Meara M, Pardo E, Poy F, Sandy P, Supko J, Sims RJ 3rd, Harmange JC, Taylor AM, Audia JE J Med Chem. 2016 Feb 4. PMID:26815195[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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