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.
| Original language | English |
|---|---|
| Pages (from-to) | 1478-1504 |
| Number of pages | 27 |
| Journal | Current Medicinal Chemistry |
| Volume | 21 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 2014 |
| Externally published | Yes |
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Keywords
- Agonist
- Chiral recognition
- Formyl peptide receptor
- G protein-coupled receptor
- Molecular modeling
- Neutrophil
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Medicine(all)
Cite this
Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition. / Schepetkin, I. A.; Khlebnikov, A. I.; Giovannoni, M. P.; Kirpotina, L. N.; Cilibrizzi, A.; Quinn, M. T.
In: Current Medicinal Chemistry, Vol. 21, No. 13, 2014, p. 1478-1504.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition
AU - Schepetkin, I. A.
AU - Khlebnikov, A. I.
AU - Giovannoni, M. P.
AU - Kirpotina, L. N.
AU - Cilibrizzi, A.
AU - Quinn, M. T.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Agonist
KW - Chiral recognition
KW - Formyl peptide receptor
KW - G protein-coupled receptor
KW - Molecular modeling
KW - Neutrophil
UR - http://www.scopus.com/inward/record.url?scp=84899864401&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899864401&partnerID=8YFLogxK
U2 - 10.2174/0929867321666131218095521
DO - 10.2174/0929867321666131218095521
M3 - Review article
VL - 21
SP - 1478
EP - 1504
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 13
ER -