Title: Development of BRD4 inhibitors as anti-inflammatory agents and antidotes for arsenicals.

Authors: Yatchang, Marina Fosso; Mathew, Bini; Srivastava, Ritesh K; Khan, Jasim; Muzaffar, Suhail; Zhang, Sixue; Wu, Mousheng; Zhai, Ling; Ruiz, Pedro; Agarwal, Anupam; Bostwick, James R; Suto, Mark J; Athar, Mohammad; Augelli-Szafran, Corinne E

Published In Bioorg Med Chem Lett, (2022 May 15)

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 ID: 35318165

MeSH Terms: Anti-Inflammatory Agents/chemistry; Antidotes/pharmacology; Arsenicals*/pharmacology; Arsenicals*/therapeutic use; Nuclear Proteins/metabolism; Transcription Factors/metabolism