The formyl peptide receptors FPR1 and FPR2 as targets for inflammatory disorders: recent advances in the development of small-molecule agonists

Xiangyan Yi; Eric Tran; Jephthah O Odiba; Cheng Xue Qin; Rebecca H Ritchie; Jonathan B Baell

doi:10.1016/j.ejmech.2023.115989

The formyl peptide receptors FPR1 and FPR2 as targets for inflammatory disorders: recent advances in the development of small-molecule agonists

Eur J Med Chem. 2024 Feb 5:265:115989. doi: 10.1016/j.ejmech.2023.115989. Epub 2023 Nov 27.

Authors

Xiangyan Yi¹, Eric Tran¹, Jephthah O Odiba¹, Cheng Xue Qin², Rebecca H Ritchie³, Jonathan B Baell⁴

Affiliations

¹ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia.
² Drug Discovery Biology, Monash Institute of Pharmaceutical Science, Monash University, Parkville, Victoria, 3052, Australia; Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria, 3004, Australia. Electronic address: Helena.Qin@monash.edu.
³ Drug Discovery Biology, Monash Institute of Pharmaceutical Science, Monash University, Parkville, Victoria, 3052, Australia; Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria, 3004, Australia. Electronic address: Rebecca.Ritchie@monash.edu.
⁴ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia. Electronic address: jonathan@lyterian.com.

PMID: 38199163
DOI: 10.1016/j.ejmech.2023.115989

Abstract

Formyl peptide receptors (FPRs) comprise a class of chemoattractant pattern recognition receptors, for which several physiological functions like host-defences, as well as the regulation of inflammatory responses, have been ascribed. With accumulating evidence that agonism of FPR1/FPR2 can confer pro-resolution of inflammation, increased attention from academia and industry has led to the discovery of new and interesting small-molecule FPR1/FPR2 agonists. Focused attention on the development of appropriate physicochemical and pharmacokinetic profiles is yielding synthesis of new compounds with promising in vivo readouts. This review presents an overview of small-molecule FPR1/FPR2 agonist medicinal chemistry developed over the past 20 years, with a particular emphasis on interrogation in the increasingly sophisticated bioassays which have been developed.

Keywords: Biased profiles; FPRs; Inflammatory disorders; Small-molecule agonists; Structure-activity relationships.

Publication types

Review

MeSH terms

Anti-Inflammatory Agents* / chemistry
Anti-Inflammatory Agents* / pharmacology
Neutrophils*
Receptors, Formyl Peptide* / agonists

Substances

Receptors, Formyl Peptide
FPR1 protein, human
FPR2 protein, human
Anti-Inflammatory Agents