2. Academic Validation
  3. Development of BRD4 inhibitors as anti-inflammatory agents and antidotes for arsenicals

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

  • Bioorg Med Chem Lett. 2022 May 15;64:128696. doi: 10.1016/j.bmcl.2022.128696.
Marina Fosso Yatchang 1,  Bini Mathew 1,  Ritesh K Srivastava 2,  Jasim Khan 2,  Suhail Muzaffar 2,  Sixue Zhang 1,  Mousheng Wu 1,  Ling Zhai 1,  Pedro Ruiz 1,  Anupam Agarwal 3,  James R Bostwick 1,  Mark J Suto 1,  Mohammad Athar 4,  Corinne E Augelli-Szafran 5
Affiliations

Affiliations

  • 1 Scientific Platforms, Southern Research, 2000 Ninth Avenue South, Birmingham, AL 35205, USA.
  • 2 UAB Research Center of Excellence in Arsenicals, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 3 UAB Research Center of Excellence in Arsenicals, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 4 UAB Research Center of Excellence in Arsenicals, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: mohammadathar@uabmc.edu.
  • 5 Scientific Platforms, Southern Research, 2000 Ninth Avenue South, Birmingham, AL 35205, USA. Electronic address: caugelli-szafran@southernresearch.org.
PMID: 35318165 DOI: 10.1016/j.bmcl.2022.128696
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.

Keywords

Antidotes; Arsenicals; Bromodomain 4; Inflammation.

Figures
Products