1. Academic Validation
  2. From Lead to Clinical Candidate: Discovery of BMS-986331 as a Potent and Selective N-Formyl Peptide Receptor 2 Agonist

From Lead to Clinical Candidate: Discovery of BMS-986331 as a Potent and Selective N-Formyl Peptide Receptor 2 Agonist

  • J Med Chem. 2026 Feb 26;69(4):4078-4089. doi: 10.1021/acs.jmedchem.5c02712.
Pravin S Shirude 1 Daniel Cheney 2 Amit K Chattopadhyay 3 Balaji Seshadri 3 Vishweshwaraiah Baligar 3 Chandrasekhar Rachamreddy 3 Sudhakara Madduri 3 Prakash Anjanappa 3 Andrew Viet 2 Meriah N Valente 2 Karen Rossi 2 Mojgan Abousleiman 2 Mei-Yin Hsu 2 Gerry Everlof 2 Volodymyr Gali 2 Yongnian Sun 2 John Allocco 2 Rongan Zhang 2 Stéphane St-Onge 4 John Lupisella 2 Xue-Qing Chen 2 Sanket Sarodaya 3 Madhu Sudhan Ravindran 1 Debarati M Tagore 1 Jignesh Nagar 3 Shailesh Dudhgaonkar 1 Sivaprasad Putlur 3 Madeleine Héroux 4 Michel Bouvier 4 Ruth R Wexler 2 Elizabeth Dierks 2 Ricardo A Garcia 2 Ellen K Kick 2 Nicholas R Wurtz 2
Affiliations

Affiliations

  • 1 Bristol Myers Squibb, Bangalore 560099, India.
  • 2 Bristol Myers Squibb, Princeton, New Jersey 08543, United States.
  • 3 Biocon Bristol Myers Squibb R&D Center (BBRC), Bangalore 560099, India.
  • 4 Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
Abstract

FPR2 belongs to a subfamily of GPCRs that play a vital role in host defense and regulation of inflammation. FPR2 modulation is proposed to enhance myocardial wound healing postmyocardial infarction, diminish adverse myocardial remodeling, and alter progression to heart failure. Herein, we report lead optimization efforts originating from our previously reported lead compound 1, delivering compound 16 (BMS-986331), which advanced into clinical trials. Compound 16 is a highly potent and selective FPR2 agonist that induces the expression and release of the pro-resolution cytokine IL-10 in both human whole blood and in acute rat models of inflammation. Moreover, chronic treatment with 16 improves cardiac structure and function in a rat heart failure model after permanent coronary artery occlusion. The physicochemical and ADMET properties of 16 combined with high potency lead to a predicted low oral dose in humans.

Figures
Products