Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition

I. A. Schepetkin, A. I. Khlebnikov, M. P. Giovannoni, L. N. Kirpotina, A. Cilibrizzi, M. T. Quinn

Research output: Contribution to journalReview articlepeer-review

29 Citations (Scopus)


Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) expressed on a variety of cell types. These receptors play an important role in the regulation of inflammatory reactions and sensing cellular damage. They have also been implicated in the pathogenesis of various diseases, including neurodegenerative diseases, cataract formation, and atherogenesis. Thus, FPR ligands, both agonists and antagonists, may represent novel therapeutics for modulating host defense and innate immunity. A variety of molecules have been identified as receptor subtype-selective and mixed FPR agonists with potential therapeutic value during last decade. This review describes our efforts along with recent advances in the identification, optimization, biological evaluation, and structure-activity relationship (SAR) analysis of small molecule non-peptide FPR agonists and antagonists, including chiral molecules. Questions regarding the interaction at the molecular level of benzimidazoles, pyrazolones, pyridazin-3(2H)-ones, N-phenylureas and other derivatives with FPR1 and FPR2 are discussed. Application of computational models for virtual screening and design of FPR ligands is also considered.

Original languageEnglish
Pages (from-to)1478-1504
Number of pages27
JournalCurrent Medicinal Chemistry
Issue number13
Publication statusPublished - 2014
Externally publishedYes


  • Agonist
  • Chiral recognition
  • Formyl peptide receptor
  • G protein-coupled receptor
  • Molecular modeling
  • Neutrophil

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Medicine(all)

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