7T3F

Development of BRD4 inhibitors as arsenicals antidotes

Summary for 7T3F

• Entry DOI: 10.2210/pdb7t3f/pdb
• Descriptor: Bromodomain-containing protein 4, 4-fluoro-3-methyl-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzene-1-sulfonamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: bromodomain-containing protein, dna damage, antidotes, brd4 inhibitors, gene regulation
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15704.05

Authors

Wu, M.,Yatchang, M.,Mathew, B.,Zhai, L.,Ruiz, P.,Bostwick, R.,Augelli-Szafran, C.E.,Suto, M.J. (deposition date: 2021-12-07, release date: 2022-08-31, Last modification date: 2023-10-18)

Primary citation

Yatchang, M.F.,Mathew, B.,Srivastava, R.K.,Khan, J.,Muzaffar, S.,Zhang, S.,Wu, M.,Zhai, L.,Ruiz, P.,Agarwal, A.,Bostwick, J.R.,Suto, M.J.,Athar, M.,Augelli-Szafran, C.E.
Development of BRD4 inhibitors as anti-inflammatory agents and antidotes for arsenicals.
Bioorg.Med.Chem.Lett., 64:128696-128696, 2022

PubMed Abstract: Arsenicals belong to the class of chemical warfare agents known as vesicants, which are highly reactive, toxic and cause robust inflammatory response. Cutaneous exposure to arsenicals causes a wide range of systemic organ damage, beginning with cutaneous injuries, and later manifest multi-organ damage and death. Thus, the development of suitable antidotes that can effectively block injury following exposure to these agents is of great importance. Bromodomain 4 (BRD4), a member of the bromodomain and extra terminal domain (BET) family, plays crucial role in regulating transcription of inflammatory, proliferation and cell cycle genes. In this context, the development of potent small molecule inhibitors of BRD4 could serve as potential antidotes for arsenicals. Herein, we describe the synthesis and biological evaluation of a series of compounds.

PubMed: 35318165
DOI: 10.1016/j.bmcl.2022.128696

Experimental method

X-RAY DIFFRACTION (1.28 Å)