7dhs

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Crystal Structure Analysis of the BRD4

Structural highlights

7dhs is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.76Å
Ligands:H8C
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.

Y06014 is a selective BET inhibitor for the treatment of prostate cancer.,Wu TB, Xiang QP, Wang C, Wu C, Zhang C, Zhang MF, Liu ZX, Zhang Y, Xiao LJ, Xu Y Acta Pharmacol Sin. 2021 Mar 2. pii: 10.1038/s41401-021-00614-7. doi:, 10.1038/s41401-021-00614-7. PMID:33654218[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Wu TB, Xiang QP, Wang C, Wu C, Zhang C, Zhang MF, Liu ZX, Zhang Y, Xiao LJ, Xu Y. Y06014 is a selective BET inhibitor for the treatment of prostate cancer. Acta Pharmacol Sin. 2021 Mar 2. pii: 10.1038/s41401-021-00614-7. doi:, 10.1038/s41401-021-00614-7. PMID:33654218 doi:http://dx.doi.org/10.1038/s41401-021-00614-7

Contents


PDB ID 7dhs

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OCA

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