| Structural highlights
Disease
[BRD4_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]
Function
[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
Publication Abstract from PubMed
A new series of quinazoline-based analogs as potent bromodomain-containing protein 4 (BRD4) inhibitors is described. The structure-activity relationships on 2- and 4-position of quinazoline ring, and the substitution at 6-position that mimic the acetylated lysine are discussed. A co-crystallized structure of 48 (CN750) with BRD4 (BD1) including key inhibitor-protein interactions is also highlighted. Together with preliminary rodent pharmacokinetic results, a new lead (65, CN427) is identified which is suitable for further lead optimization.
Discovery and lead identification of quinazoline-based BRD4 inhibitors.,Yang SM, Urban DJ, Yoshioka M, Strovel JW, Fletcher S, Wang AQ, Xu X, Shah P, Hu X, Hall MD, Jadhav A, Maloney DJ Bioorg Med Chem Lett. 2018 Nov 15;28(21):3483-3488. doi:, 10.1016/j.bmcl.2018.08.039. Epub 2018 Aug 31. PMID:30268702[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
- ↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
- ↑ Yang SM, Urban DJ, Yoshioka M, Strovel JW, Fletcher S, Wang AQ, Xu X, Shah P, Hu X, Hall MD, Jadhav A, Maloney DJ. Discovery and lead identification of quinazoline-based BRD4 inhibitors. Bioorg Med Chem Lett. 2018 Nov 15;28(21):3483-3488. doi:, 10.1016/j.bmcl.2018.08.039. Epub 2018 Aug 31. PMID:30268702 doi:http://dx.doi.org/10.1016/j.bmcl.2018.08.039
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