title: Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition.
abstract: 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.
authors.forename: I A
authors.initials: IA
authors.lastname: Schepetkin
authors.forename: A I
authors.initials: AI
authors.lastname: Khlebnikov
authors.forename: M P
authors.initials: MP
authors.lastname: Giovannoni
authors.forename: L N
authors.initials: LN
authors.lastname: Kirpotina
authors.forename: A
authors.initials: A
authors.lastname: Cilibrizzi
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT 59717, USA. mquinn@montana.edu.
authors.forename: M T
authors.initials: MT
authors.lastname: Quinn
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D044042:Receptors, Formyl Peptide / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D044042:Receptors, Formyl Peptide; D054852:Small Molecule Libraries