Top ▲


Click here for help

Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 222

Nomenclature: FPR1

Family: Formylpeptide receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 350 19q13.41 FPR1 formyl peptide receptor 1 4,58
Mouse 7 364 17 10.63 cM Fpr1 formyl peptide receptor 1 24
Rat 7 355 1q12 Fpr1 formyl peptide receptor 1 56
Previous and Unofficial Names Click here for help
NFPR | FPR | formyl peptide receptor 1 | fMLF-R
Database Links Click here for help
Specialist databases
GPCRdb fpr1_human (Hs), fpr1_mouse (Mm)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands Click here for help
annexin I {Sp: Human} , annexin I {Sp: Mouse} , annexin I {Sp: Rat}
cathepsin G {Sp: Human} , cathepsin G {Sp: Mouse} , cathepsin G {Sp: Rat}
Potency order of endogenous ligands (Human)
fMet-Leu-Phe > cathepsin G (CTSG, P08311) > annexin I (ANXA1, P04083)  [46,81]

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
fMet-Leu-Phe-Ile-Ile-Lys-FITC Peptide Ligand is labelled Mm Full agonist 8.6 pKd 33
pKd 8.6 [33]
[3H]fMet-Leu-Phe Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 7.6 – 9.3 pKd 40
pKd 7.6 – 9.3 (Kd 2.51x10-8 – 5x10-10 M) [40]
[125I]cathepsin G (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 7.0 pKd 81
pKd 7.0 [81]
fMet-Ile-Val-Thr-Leu-Phe Peptide Click here for species-specific activity table Mm Full agonist 10.7 pEC50 33
pEC50 10.7 [33]
fMet-Ile-Phe-Leu Peptide Hs Full agonist 10.5 pEC50 69
pEC50 10.5 [69]
fMet-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 10.1 – 10.2 pEC50 23,78
pEC50 10.1 – 10.2 [23,78]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Mm Full agonist 10.0 pEC50 33
pEC50 10.0 [33]
fMet-Ile-Phe-Leu Peptide Mm Full agonist 9.5 pEC50 33
pEC50 9.5 [33]
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 9.0 pEC50 43
pEC50 9.0 [43]
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 9.0 pEC50 33-34
pEC50 9.0 [33-34]
Met-Met-Trp-Leu-Leu Peptide Hs Full agonist 9.0 pEC50 13
pEC50 9.0 [13]
fMet-Met-Trp-Leu-Leu Peptide Hs Full agonist 9.0 pEC50 13
pEC50 9.0 [13]
pyrazolone, 1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Full agonist 8.7 pEC50 33
pEC50 8.7 [33]
fMet-Ile-Val-Ile-Leu Peptide Hs Full agonist 8.7 pEC50 68
pEC50 8.7 [68]
fMet-Ile-Val-Thr-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 8.6 pEC50 68
pEC50 8.6 [68]
T20(DP178) Peptide Hs Full agonist 8.3 pEC50 32,80
pEC50 8.3 [32,80]
fMet-Leu-Phe-Glu Peptide Mm Full agonist 8.2 pEC50 33
pEC50 8.2 [33]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 8.0 pEC50 68
pEC50 8.0 [68]
AG-14 Small molecule or natural product Hs Full agonist 7.4 pEC50 71
pEC50 7.4 [71]
annexin I {Sp: Human} Peptide Mm Full agonist 6.6 pEC50 18,65
pEC50 6.6 [18,65]
BMS-986235 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 6.4 pEC50 3
pEC50 6.4 (EC50 4x10-7 M) [3]
BMS-986235 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Agonist 6.3 pEC50 3
pEC50 6.3 (EC50 5x10-7 M) [3]
gG-2p20 Peptide Hs Full agonist 6.2 – 6.3 pEC50 6
pEC50 6.2 – 6.3 [6]
compound R-(-)-5f [PMID: 22607879] Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 pEC50 16
pEC50 6.0 (EC50 9.4x10-7 M) [16]
annexin I-(2-26) {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 5.8 – 6.1 pEC50 27,84
pEC50 5.8 – 6.1 [27,84]
AG-11/03 Small molecule or natural product Hs Full agonist 5.6 pEC50 38
pEC50 5.6 [38]
AG-09/1 Small molecule or natural product Hs Full agonist 5.6 pEC50 39
pEC50 5.6 [39]
fMet-Leu-Phe Peptide Mm Full agonist 4.7 pEC50 31,79
pEC50 4.7 [31,79]
spinorphin Peptide Mm Partial agonist 3.9 pEC50 48
pEC50 3.9 [48]
View species-specific agonist tables
Agonist Comments
FPR1-mediated neutrophil functions have different requirements for agonist concentrations, from low (chemotaxis) to high (superoxide generation). Some early studies of fMet-Leu-Phe were conducted on rabbit neutrophils [10,24]. The annexin I peptides include Ac2-12, Ac2-26 and Ac9-25. These peptides bind to both FPR1 and FPR2 with similar affinities, and therefore non-selective according to IUPHAR standard [18,27,37,84]. T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of FPR1 [80]. AG-14 (1,3-benzodioxolane-5-carboxylic acid 4`-benzyloxy-3`-methoxybenzylidene-hydrazide) represents a novel small-molecule agonist of FPR1. Selected chiral compounds are potent mixed FPR1/FPR2 agonists, among which R-(-)-forms generally exhibits higher activity than the S-(+)-enantiomers [16]. Benzimidazole derivatives include 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derivatives and 2-(5-alkoxybenzimidazol-2-ylthio)-N-phenylacetamide derivatives, among which FPR1-specific agonists are AG-09/1, AG-09/2, AG-09/13, AG-09/18, AG-09/19, AG-09/21, AG-11/03, AG-11/05 and AG-11/23, while the other compounds tested in the series are mixed FPR1/FPR2 agonists or FPR2-specific agonists [38-39]. Despite acting as a calcium-mobilizing agonist at mouse Fpr1, spinorphin is a weak chemotactic agonist and effectively blocks neutrophil chemotaxis induced by fMLF at concentrations selective for mouse Fpr1 [48].
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]CHIPS Peptide Ligand is labelled Ligand is radioactive Hs Antagonist 7.5 pKd 30
pKd 7.5 [30]
3570-0208 [PMID:19807662] Small molecule or natural product Hs Antagonist 7.0 pKi 2
pKi 7.0 [2]
cyclosporin H Peptide Hs Antagonist 6.1 – 7.1 pKi 86,89
pKi 6.1 – 7.1 (Ki 7.94x10-7 – 7.94x10-8 M) [86,89]
t-Boc-FLFLF Peptide Click here for species-specific activity table Hs Antagonist 6.0 – 6.5 pKi 86
pKi 6.0 – 6.5 [86]
chenodeoxycholic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.0 pKi 15
pKi 4.0 [15]
deoxycholic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.0 pKi 14
pKi 4.0 [14]
cyclosporin A Peptide Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.2 – 6.3 pEC50 88
pEC50 6.2 – 6.3 [88]
BVT173187 Small molecule or natural product Hs Antagonist 7.0 pIC50 12
pIC50 7.0 [12]
i-Boc-Met-Leu-Phe Peptide Hs Antagonist 6.6 pIC50 19
pIC50 6.6 [19]
t-Boc-FLFLF Peptide Click here for species-specific activity table Hs Antagonist 6.6 pIC50 85
pIC50 6.6 [85]
diamide 7 Small molecule or natural product Hs Antagonist 6.5 pIC50 83
pIC50 6.5 [83]
methionine benzimidazole 6 Small molecule or natural product Hs Antagonist 6.3 pIC50 83
pIC50 6.3 [83]
t-Boc-Met-Leu-Phe Peptide Hs Antagonist 6.2 pIC50 85
pIC50 6.2 [85]
group E 1682-2106 [PMID:16118363] Small molecule or natural product Hs Antagonist 5.3 pIC50 21
pIC50 5.3 [21]
sufinpyrazone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.0 pIC50 90
pIC50 5.0 [90]
spinorphin Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Antagonist 4.3 pIC50 48,58
pIC50 4.3 [48,58]
Antagonist Comments
CHIPS is a 14.1 kDa protein found in more than half of the clinical strains of Staphylococcus aureus. Its N-terminal peptides of various lengths are also FPR1 antagonists but are 3 orders of magnitude less potent [30]. Boc-Met-Leu-Phe is also termed Boc1, and Boc-Phe-Leu-Phe-Leu-Phe is referred to as Boc2. The latter is an antagonist of both FPR1 and FPR2, and therefore is considered non-selective. Spinorphin is an endogenous peptide with the sequence of Leu-Val-Val-Tyr-Pro-Trp-Thr. BVT173187 (3,5-dichloro-N-(2-chloro-5-methyl-phenyl)-2-hydroxy-benzamide) fulfills the criteria for an FPR1 inhibitor selective for FPR1 over FPR2, and the potency is the same as that of cyclosporine H, but signaling through C5aR and CXCR (recognizing IL8) is also affected by BVT173187.
Immunopharmacology Comments
The primary function of FPR1 is recognition of formylpeptides. Detection of bacterial N-formylpeptides via FPR1 activates immune-cell chemotaxis and cytokine release, making this GPCR an important component of the host defense mechanism.

Osei-Owusu et al. (2019) demonstrated that FPR1 on immune cells is the target of the needle cap protein (LcrV; Uniprot accession P0C7U7) of Yersinia pestis (the plague bacterium), via which the bacteria destroy host immune cells [61]. By eliminating host cellular defences Y. pestis creates a more hospitable environment in which it can survive and reproduce. In the same study, the team also identified a candidate resistance mutation in human FPR1 that provides neutrophils with some protection from Y. pestis-induced destruction.
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   neutrophil (CL:0000775)
Comment:  FPR1 on neutrophils is a physiologically relevant plague receptor. It is exploited by Y. pestis to deliver effector proteins of the bacterium's conserved type III secretion system to host cells.
References:  61
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
References:  1,28,57,76
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Calcium channel
Comments:  Increase of intracellular Ca2+ level results in opening of membrane Ca2+ channel in fMLF-stimulated cells. This response is secondary to release of Ca2+ from intracelluar stores.
References:  50,59,64,67
Tissue Distribution Click here for help
Non-myeloid cells: Low levels of FPR1 transcript and protein are found in hepatocytes, platelets, endothelial cells, astrocytes, microglial cells, vascular smooth muscle cells, and fibroblasts. Using a polyclonal Ab, FPR1 expression is detected in thyroid, adrenal, motor and sensory neurons, cerebellar systems, and colon.
Species:  Human
Technique:  Immunocytochemistry
References:  5,17,42,44,54
Myeloid cells: FPR1 is primarily expressed in neutrophils, monocytes and macrophages. It is also found in eosinophils and basophils. FPR1 is not found on myeloblast cell surface but emerges gradually through stages of neutrophil maturation. Promyelocytic leukemia cell lines such as HL-60 may be differentiated to induce FPR1 expression. There is an intracellular pool of FPR1 in neutrophil granules that can be mobilized for cell surface expression.
Species:  Human
Technique:  Radioligand binding
References:  73,78,87,91
Expression Datasets Click here for help

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays Click here for help
Activation of PLA2, resulting in the generation of arachidonic acid.
Species:  Human
Tissue:  neutrophils
Response measured:  Arachidonic acid release
References:  9,53
Agonist-induced incorporation of non-hydrolyzable GTP analogs. This assay reflects activation of the receptor-coupled Gi protien, and can be blocked by pertussis toxin treatment of the cells
Species:  Human
Tissue:  Neutrophils, FPR1-expressing cell lines
Response measured:  Increase of [35S]-GTPγS in precipitated Gi protein
References:  9,74
Agonist-induced phosphoinositide metabolism. This assay reflects FPR1-mediated PLCbeta activation, which is downstream of Gi protein activation. The activation of PLCbeta is mediated by Gbeta/gamma subunits.
Species:  Human
Tissue:  Neutrophils, leukemia cell lines expressing FPR1
Response measured:  PIP2 hydrolysis
References:  41,77,82
Activation of PLD and formation of phosphatidate
Species:  Human
Tissue:  Neutrophils
Response measured:  [3H]glycerol-labeled phosphatidate formation
References:  8,47,63
Ca2+ mobilization. This function is induced when FPR1 is activated by agonists. The rise of intracellular Ca2+ consists of release of Ca2+ from intracellular stores and Ca2+ influx. The function is secondary to PLCbeta activation and IP3 production, and be reproduced in various cells.
Species:  Human
Tissue:  Neutrophils and various transfected cells
Response measured:  Intracellular Ca2+ concentration
References:  50,59,64,67
Physiological Functions Click here for help
Degranulation. Release of lysosozyme and beta-glucuronidase has been used in early studies of FPR1 activation. This function is reproducible with exogenously expressed FPR1.
Species:  Human
Tissue:  neutrophils
References:  7,78
Adhesion. Formylpeptides such as fMLF increase neutrophil adhesion to coated surface, believed to result from increased integrin activities.
Species:  Human
Tissue:  Myeloid cells, neutrophils
References:  11,35,55
One study indicates that fMLF has anti-nociceptive effect in mouse formalin test of nociceptive stimulation. Some of the Annexin I peptides also reduced nociceptive response.
Species:  Mouse
Tissue:  Whole animal
References:  66
Chemotaxis: Formylpeptides stimulate chemotaxis of phagocytes at low concentrations . This function is confirmed using exogenously expressed FPR1. Chemotaxis is responsible for neutrophil accumulation at sites of acute bacterial infection.
Species:  Human
Tissue:  Neutrophils from human and rabbits.
References:  23,72,78,91
Physiological Consequences of Altering Gene Expression Click here for help
Silencing of the human FPR1 gene by siRNA leads to impaired chemotaxis and calcium mobilization in transfected cells, and reduced superoxide secretion in macrophages, when challenged with fMLF.
Species:  Human
Tissue:  Glioma cell line
Technique:  RNAi
References:  45
Deletion of the mouse FPR1 gene results in compromised immunity to Listeria monocytogenes infection, manifested as reduced ability of bacteria clearance and increased mortality rate. Neutrophils from the knockout mice respond poorly to fMLF.
Species:  Mouse
Tissue:  Neutrophils
Technique:  Gene targeting in embryonic stem cells
References:  25
Fpr1 (-/-) mice exhibits increased exploratory activity, reduced anxiety-like behaviour, and impaired fear memory, but normal spatial memory and learning capacity.
Species:  Mouse
Tissue:  Brain
Technique:  Gene targeting in embryonic stem cells
References:  26
Deficiency in mFpr1 and mFpr2 exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide.
Species:  Mouse
Tissue:  Neutrophils
Technique:  Gene targeting in embryonic stem cells
References:  49
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:107443  MP:0002419 abnormal innate immunity PMID: 9989980 
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:107443  MP:0008720 impaired neutrophil migration PMID: 9989980 
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:107443  MP:0002412 increased susceptibility to bacterial infection PMID: 9989980 
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:107443  MP:0009788 increased susceptibility to bacterial infection induced morbidity/mortality PMID: 9989980 
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The relatively rare 348T/T genotype is associated with significantly impaired PMN chemotaxis and an increased risk for developing aggressive periodontitis in African Americans.
References:  52
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Single nucleotide polymorphisms (SNPs) have been identified in the FPR1 gene. These SNPs result in FPR variants with the following changes: I11T, V101L, R190W, N192K, A346E. Genetic analysis showed association of the N192K and R190W with the risk of having aggressive periodontitis.
References:  20,51,70
Type:  Single nucleotide polymorphism
Species:  Human
Description:  It was reported that juvenile periodontitis patients, whose neutrophils respond poorly to fMLF, carry SNPs that cause changes in F110(S) and C126W. Test of the FPR1 variants in transfected cells found defective chemotaxis and degranulation in response to fMLF, but normal cell surface expression. However, the accuracy of the original SNP study could not be confirmed.
References:  20,29,36,60,75
Type:  Single nucleotide polymorphism
Species:  Human
Description:  FPR1 C32T SNP interacts with age, is associated with higher and a 5 years increase of BP levels in healthy individuals aged less than 45 years.
References:  22
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Asp192Lys polymorphism in FPR1 is significantly associated with increased susceptibility to stomach cancer among the elderly Japanese population.
Amino acid change:  D192K
References:  62


Show »

1. Amatruda TT, Dragas-Graonic S, Holmes R, Perez HD. (1995) Signal transduction by the formyl peptide receptor. Studies using chimeric receptors and site-directed mutagenesis define a novel domain for interaction with G-proteins. J Biol Chem, 270 (47): 28010-3. [PMID:7499283]

2. Arterburn JB, Oprea TI, Prossnitz ER, Edwards BS, Sklar LA. (2009) Discovery of selective probes and antagonists for G-protein-coupled receptors FPR/FPRL1 and GPR30. Curr Top Med Chem, 9 (13): 1227-36. [PMID:19807662]

3. Asahina Y, Wurtz NR, Arakawa K, Carson N, Fujii K, Fukuchi K, Garcia R, Hsu MY, Ishiyama J, Ito B et al.. (2020) Discovery of BMS-986235/LAR-1219: A Potent Formyl Peptide Receptor 2 (FPR2) Selective Agonist for the Prevention of Heart Failure. J Med Chem, 63 (17): 9003-9019. [PMID:32407089]

4. Bao L, Gerard NP, Eddy RL Jr, Shows TB, Gerard C. (1992) Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. Genomics, 13: 437-440. [PMID:1612600]

5. Becker EL, Forouhar FA, Grunnet ML, Boulay F, Tardif M, Bormann BJ, Sodja D, Ye RD, Woska JR, Murphy PM. (1998) Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells. Cell Tissue Res, 292 (1): 129-35. [PMID:9506920]

6. Bellner L, Thorén F, Nygren E, Liljeqvist JA, Karlsson A, Eriksson K. (2005) A proinflammatory peptide from herpes simplex virus type 2 glycoprotein G affects neutrophil, monocyte, and NK cell functions. J Immunol, 174 (4): 2235-41. [PMID:15699157]

7. Bentwood BJ, Henson PM. (1980) The sequential release of granule constitutents from human neutrophils. J Immunol, 124 (2): 855-62. [PMID:6153206]

8. Billah MM, Eckel S, Mullmann TJ, Egan RW, Siegel MI. (1989) Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phosphatidate phosphohydrolase in signal transduction. J Biol Chem, 264 (29): 17069-77. [PMID:2793844]

9. Bokoch GM, Gilman AG. (1984) Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. Cell, 39 (2 Pt 1): 301-8. [PMID:6094010]

10. Boulay F, Tardif M, Brouchon L, Vignais P. (1990) Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA. Biochem Biophys Res Commun, 168 (3): 1103-9. [PMID:2161213]

11. Campbell JJ, Qin S, Bacon KB, Mackay CR, Butcher EC. (1996) Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells. J Cell Biol, 134 (1): 255-66. [PMID:8698820]

12. Cevik-Aras H, Kalderén C, Jenmalm Jensen A, Oprea T, Dahlgren C, Forsman H. (2012) A non-peptide receptor inhibitor with selectivity for one of the neutrophil formyl peptide receptors, FPR 1. Biochem Pharmacol, 83 (12): 1655-62. [PMID:22410002]

13. Chen J, Bernstein HS, Chen M, Wang L, Ishii M, Turck CW, Coughlin SR. (1995) Tethered ligand library for discovery of peptide agonists. J Biol Chem, 270 (40): 23398-401. [PMID:7559498]

14. Chen X, Mellon RD, Yang L, Dong H, Oppenheim JJ, Howard OM. (2002) Regulatory effects of deoxycholic acid, a component of the anti-inflammatory traditional Chinese medicine Niuhuang, on human leukocyte response to chemoattractants. Biochem Pharmacol, 63 (3): 533-41. [PMID:11853704]

15. Chen X, Yang D, Shen W, Dong HF, Wang JM, Oppenheim JJ, Howard MZ. (2000) Characterization of chenodeoxycholic acid as an endogenous antagonist of the G-coupled formyl peptide receptors. Inflamm Res, 49 (12): 744-55. [PMID:11211928]

16. Cilibrizzi A, Schepetkin IA, Bartolucci G, Crocetti L, Dal Piaz V, Giovannoni MP, Graziano A, Kirpotina LN, Quinn MT, Vergelli C. (2012) Synthesis, enantioresolution, and activity profile of chiral 6-methyl-2,4-disubstituted pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists. Bioorg Med Chem, 20 (12): 3781-92. [PMID:22607879]

17. Czapiga M, Gao JL, Kirk A, Lekstrom-Himes J. (2005) Human platelets exhibit chemotaxis using functional N-formyl peptide receptors. Exp Hematol, 33 (1): 73-84. [PMID:15661400]

18. D'Acquisto F, Paschalidis N, Sampaio AL, Merghani A, Flower RJ, Perretti M. (2007) Impaired T cell activation and increased Th2 lineage commitment in Annexin-1-deficient T cells. Eur J Immunol, 37 (11): 3131-42. [PMID:17948261]

19. Derian CK, Solomon HF, Higgins 3rd JD, Beblavy MJ, Santulli RJ, Bridger GJ, Pike MC, Kroon DJ, Fischman AJ. (1996) Selective inhibition of N-formylpeptide-induced neutrophil activation by carbamate-modified peptide analogues. Biochemistry, 35 (4): 1265-9. [PMID:8573582]

20. Eckhardt K, Roth P, Günter T, Schmidt S, Feuerstein TJ. (2003) Differential effects of K(ATP) channel blockers on [(3)H]-noradrenaline overflow after short- and long-term exposure to (+)-oxaprotiline or desipramine. Naunyn Schmiedebergs Arch Pharmacol, 367 (2): 168-75. [PMID:12595958]

21. Edwards BS, Bologa C, Young SM, Balakin KV, Prossnitz ER, Savchuck NP, Sklar LA, Oprea TI. (2005) Integration of virtual screening with high-throughput flow cytometry to identify novel small molecule formylpeptide receptor antagonists. Mol Pharmacol, 68 (5): 1301-10. [PMID:16118363]

22. El Shamieh S, Herbeth B, Azimi-Nezhad M, Benachour H, Masson C, Visvikis-Siest S. (2012) Human formyl peptide receptor 1 C32T SNP interacts with age and is associated with blood pressure levels. Clin Chim Acta, 413 (1-2): 34-8. [PMID:21144844]

23. Freer RJ, Day AR, Radding JA, Schiffmann E, Aswanikumar S, Showell HJ, Becker EL. (1980) Further studies on the structural requirements for synthetic peptide chemoattractants. Biochemistry, 19 (11): 2404-10. [PMID:7387981]

24. Gao JL, Chen H, Filie JD, Kozak CA, Murphy PM. (1998) Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse. Genomics, 51 (2): 270-6. [PMID:9722950]

25. Gao JL, Lee EJ, Murphy PM. (1999) Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor. J Exp Med, 189 (4): 657-62. [PMID:9989980]

26. Gao JL, Schneider EH, Dimitrov EL, Haun F, Pham TM, Mohammed AH, Usdin TB, Murphy PM. (2011) Reduced fear memory and anxiety-like behavior in mice lacking formylpeptide receptor 1. Behav Genet, 41 (5): 724-33. [PMID:21484271]

27. Gavins FN, Yona S, Kamal AM, Flower RJ, Perretti M. (2003) Leukocyte antiadhesive actions of annexin 1: ALXR- and FPR-related anti-inflammatory mechanisms. Blood, 101 (10): 4140-7. [PMID:12560218]

28. Gilman AG. (1987) G proteins: transducers of receptor-generated signals. Annu Rev Biochem, 56: 615-49. [PMID:3113327]

29. Gwinn MR, Sharma A, De Nardin E. (1999) Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis. J Periodontol, 70 (10): 1194-201. [PMID:10534074]

30. Haas PJ, de Haas CJ, Kleibeuker W, Poppelier MJ, van Kessel KP, Kruijtzer JA, Liskamp RM, van Strijp JA. (2004) N-terminal residues of the chemotaxis inhibitory protein of Staphylococcus aureus are essential for blocking formylated peptide receptor but not C5a receptor. J Immunol, 173 (9): 5704-11. [PMID:15494522]

31. Hartt JK, Barish G, Murphy PM, Gao JL. (1999) N-formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two N-formylpeptide receptor (FPR) subtypes. Molecular characterization of FPR2, a second mouse neutrophil FPR. J Exp Med, 190 (5): 741-7. [PMID:10477558]

32. Hartt JK, Liang T, Sahagun-Ruiz A, Wang JM, Gao JL, Murphy PM. (2000) The HIV-1 cell entry inhibitor T-20 potently chemoattracts neutrophils by specifically activating the N-formylpeptide receptor. Biochem Biophys Res Commun, 272 (3): 699-704. [PMID:10860818]

33. He HQ, Liao D, Wang ZG, Wang ZL, Zhou HC, Wang MW, Ye RD. (2013) Functional characterization of three mouse formyl peptide receptors. Mol Pharmacol, 83 (2): 389-98. [PMID:23160941]

34. He R, Tan L, Browning DD, Wang JM, Ye RD. (2000) The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor. J Immunol, 165 (8): 4598-605. [PMID:11035102]

35. Honda S, Campbell JJ, Andrew DP, Engelhardt B, Butcher BA, Warnock RA, Ye RD, Butcher EC. (1994) Ligand-induced adhesion to activated endothelium and to vascular cell adhesion molecule-1 in lymphocytes transfected with the N-formyl peptide receptor. J Immunol, 152 (8): 4026-35. [PMID:7511663]

36. Jones BE, Miettinen HM, Jesaitis AJ, Mills JS. (2003) Mutations of F110 and C126 of the formyl peptide receptor interfere with G-protein coupling and chemotaxis. J Periodontol, 74 (4): 475-84. [PMID:12747452]

37. Karlsson J, Fu H, Boulay F, Dahlgren C, Hellstrand K, Movitz C. (2005) Neutrophil NADPH-oxidase activation by an annexin AI peptide is transduced by the formyl peptide receptor (FPR), whereas an inhibitory signal is generated independently of the FPR family receptors. J Leukoc Biol, 78 (3): 762-71. [PMID:15951351]

38. Khlebnikov AI, Schepetkin IA, Kirpotina LN, Brive L, Dahlgren C, Jutila MA, Quinn MT. (2012) Molecular docking of 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derived small-molecule agonists of human formyl peptide receptor 1. J Mol Model, 18 (6): 2831-43. [PMID:22127612]

39. Kirpotina LN, Khlebnikov AI, Schepetkin IA, Ye RD, Rabiet MJ, Jutila MA, Quinn MT. (2010) Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition. Mol Pharmacol, 77 (2): 159-70. [PMID:19903830]

40. Koo C, Lefkowitz RJ, Snyderman R. (1982) The oligopeptide chemotactic factor receptor on human polymorphonuclear leukocyte membranes exists in two affinity states. Biochem Biophys Res Commun, 106: 442-449. [PMID:6285921]

41. Krause KH, Schlegel W, Wollheim CB, Andersson T, Waldvogel FA, Lew PD. (1985) Chemotactic peptide activation of human neutrophils and HL-60 cells. Pertussis toxin reveals correlation between inositol trisphosphate generation, calcium ion transients, and cellular activation. J Clin Invest, 76 (4): 1348-54. [PMID:3877077]

42. Lacy M, Jones J, Whittemore SR, Haviland DL, Wetsel RA, Barnum SR. (1995) Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. J Neuroimmunol, 61 (1): 71-8. [PMID:7560015]

43. Le Y, Gong W, Li B, Dunlop NM, Shen W, Su SB, Ye RD, Wang JM. (1999) Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation. J Immunol, 163 (12): 6777-84. [PMID:10586077]

44. Le Y, Hu J, Gong W, Shen W, Li B, Dunlop NM, Halverson DO, Blair DG, Wang JM. (2000) Expression of functional formyl peptide receptors by human astrocytoma cell lines. J Neuroimmunol, 111 (1-2): 102-8. [PMID:11063827]

45. Le Y, Iribarren P, Zhou Y, Gong W, Hu J, Zhang X, Wang JM. (2004) Silencing the formylpeptide receptor FPR by short-interfering RNA. Mol Pharmacol, 66 (4): 1022-8. [PMID:15258259]

46. Le Y, Murphy PM, Wang JM. (2002) Formyl-peptide receptors revisited. Trends Immunol, 23 (11): 541-8. [PMID:12401407]

47. Lehman N, Di Fulvio M, McCray N, Campos I, Tabatabaian F, Gomez-Cambronero J. (2006) Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2. Blood, 108 (10): 3564-72. [PMID:16873675]

48. Liang TS, Gao JL, Fatemi O, Lavigne M, Leto TL, Murphy PM. (2001) The endogenous opioid spinorphin blocks fMet-Leu-Phe-induced neutrophil chemotaxis by acting as a specific antagonist at the N-formylpeptide receptor subtype FPR. J Immunol, 167 (11): 6609-14. [PMID:11714831]

49. Liu M, Chen K, Yoshimura T, Liu Y, Gong W, Wang A, Gao JL, Murphy PM, Wang JM. (2012) Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes. Sci Rep, 2: 786. [PMID:23139859]

50. Mahomed AG, Anderson R. (2000) Activation of human neutrophils with chemotactic peptide, opsonized zymosan and the calcium ionophore A23187, but not with a phorbol ester, is accompanied by efflux and store-operated influx of calcium. Inflammation, 24 (6): 559-69. [PMID:11128053]

51. Maney P, Emecen P, Mills JS, Walters JD. (2009) Neutrophil formylpeptide receptor single nucleotide polymorphism 348T>C in aggressive periodontitis. J Periodontol, 80 (3): 492-8. [PMID:19254133]

52. Maney P, Walters JD. (2009) Formylpeptide receptor single nucleotide polymorphism 348T>C and its relationship to polymorphonuclear leukocyte chemotaxis in aggressive periodontitis. J Periodontol, 80 (9): 1498-505. [PMID:19722801]

53. Marshall J, Krump E, Lindsay T, Downey G, Ford DA, Zhu P, Walker P, Rubin B. (2000) Involvement of cytosolic phospholipase A2 and secretory phospholipase A2 in arachidonic acid release from human neutrophils. J Immunol, 164 (4): 2084-91. [PMID:10657662]

54. McCoy R, Haviland DL, Molmenti EP, Ziambaras T, Wetsel RA, Perlmutter DH. (1995) N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation. J Exp Med, 182 (1): 207-17. [PMID:7540650]

55. Miettinen HM, Gripentrog JM, Jesaitis AJ. (1998) Chemotaxis of chinese hamster ovary cells expressing the human neutrophil formyl peptide receptor: role of signal transduction molecules and alpha5beta1 integrin. J Cell Sci, 111 ( Pt 14): 1921-8. [PMID:9645940]

56. Morley AD, King S, Roberts B, Lever S, Teobald B, Fisher A, Cook T, Parker B, Wenlock M, Phillips C et al.. (2012) Lead optimisation of pyrazoles as novel FPR1 antagonists. Bioorg Med Chem Lett, 22 (1): 532-6. [PMID:22094028]

57. Mullmann TJ, Cheewatrakoolpong B, Anthes JC, Siegel MI, Egan RW, Billah MM. (1993) Phospholipase C and phospholipase D are activated independently of each other in chemotactic peptide-stimulated human neutrophils. J Leukoc Biol, 53 (6): 630-5. [PMID:8315346]

58. Murphy PM, Ozçelik T, Kenney RT, Tiffany HL, McDermott D, Francke U. (1992) A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. J Biol Chem, 267 (11): 7637-43. [PMID:1373134]

59. Naccache PH, Showell HJ, Becker EL, Sha'afi RI. (1977) Transport of sodium, potassium, and calcium across rabbit polymorphonuclear leukocyte membranes. Effect of chemotactic factor. J Cell Biol, 73 (2): 428-44. [PMID:558197]

60. Nanamori M, He R, Sang H, Ye RD. (2004) Normal cell surface expression and selective loss of functions resulting from Phe110 to Ser and Cys126 to Trp substitutions in the formyl peptide receptor. Immunol Invest, 33 (2): 193-212. [PMID:15195697]

61. Osei-Owusu P, Charlton TM, Kim HK, Missiakas D, Schneewind O. (2019) FPR1 is the plague receptor on host immune cells. Nature, 574 (7776): 57-62. [PMID:31534221]

62. Otani T, Ikeda S, Lwin H, Arai T, Muramatsu M, Sawabe M. (2011) Polymorphisms of the formylpeptide receptor gene (FPR1) and susceptibility to stomach cancer in 1531 consecutive autopsy cases. Biochem Biophys Res Commun, 405 (3): 356-61. [PMID:21216225]

63. Pai JK, Siegel MI, Egan RW, Billah MM. (1988) Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes. J Biol Chem, 263 (25): 12472-7. [PMID:3165977]

64. Partida-Sánchez S, Cockayne DA, Monard S, Jacobson EL, Oppenheimer N, Garvy B, Kusser K, Goodrich S, Howard M, Harmsen A et al.. (2001) Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med, 7 (11): 1209-16. [PMID:11689885]

65. Perretti M, Getting SJ, Solito E, Murphy PM, Gao JL. (2001) Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. Am J Pathol, 158 (6): 1969-73. [PMID:11395373]

66. Pieretti S, Di Giannuario A, De Felice M, Perretti M, Cirino G. (2004) Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides. Pain, 109 (1-2): 52-63. [PMID:15082126]

67. Pozzan T, Lew DP, Wollheim CB, Tsien RY. (1983) Is cytosolic ionized calcium regulating neutrophil activation?. Science, 221 (4618): 1413-5. [PMID:6310757]

68. Rabiet MJ, Huet E, Boulay F. (2005) Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur J Immunol, 35 (8): 2486-95. [PMID:16025565]

69. Rot A, Henderson LE, Copeland TD, Leonard EJ. (1987) A series of six ligands for the human formyl peptide receptor: tetrapeptides with high chemotactic potency and efficacy. Proc Natl Acad Sci USA, 84 (22): 7967-71. [PMID:2825171]

70. Sahagun-Ruiz A, Colla JS, Juhn J, Gao JL, Murphy PM, McDermott DH. (2001) Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R. Genes Immun, 2 (6): 335-42. [PMID:11607790]

71. Schepetkin IA, Kirpotina LN, Khlebnikov AI, Quinn MT. (2007) High-throughput screening for small-molecule activators of neutrophils: identification of novel N-formyl peptide receptor agonists. Mol Pharmacol, 71 (4): 1061-74. [PMID:17229869]

72. Schiffmann E, Corcoran BA, Wahl SM. (1975) N-formylmethionyl peptides as chemoattractants for leucocytes. Proc Natl Acad Sci USA, 72 (3): 1059-62. [PMID:1093163]

73. Schiffmann E, Showell HV, Corcoran BA, Ward PA, Smith E, Becker EL. (1975) The isolation and partial characterization of neutrophil chemotactic factors from Escherichia coli. J Immunol, 114 (6): 1831-7. [PMID:165239]

74. Schreiber RE, Prossnitz ER, Ye RD, Cochrane CG, Jesaitis AJ, Bokoch GM. (1993) Reconstitution of recombinant N-formyl chemotactic peptide receptor with G protein. J Leukoc Biol, 53 (4): 470-4. [PMID:8482927]

75. Seifert R, Wenzel-Seifert K. (2001) Defective Gi protein coupling in two formyl peptide receptor mutants associated with localized juvenile periodontitis. J Biol Chem, 276 (45): 42043-9. [PMID:11559706]

76. Sergeant S, McPhail LC. (2007) Measurement of phospholipid metabolism in intact neutrophils. Methods Mol Biol, 412: 69-83. [PMID:18453106]

77. Sharma VP, DesMarais V, Sumners C, Shaw G, Narang A. (2008) Immunostaining evidence for PI(4,5)P2 localization at the leading edge of chemoattractant-stimulated HL-60 cells. J Leukoc Biol, 84 (2): 440-7. [PMID:18477691]

78. Showell HJ, Freer RJ, Zigmond SH, Schiffmann E, Aswanikumar S, Corcoran B, Becker EL. (1976) The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med, 143 (5): 1154-69. [PMID:1262785]

79. Southgate EL, He RL, Gao JL, Murphy PM, Nanamori M, Ye RD. (2008) Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophils. J Immunol, 181 (2): 1429-37. [PMID:18606697]

80. Su SB, Gong WH, Gao JL, Shen WP, Grimm MC, Deng X, Murphy PM, Oppenheim JJ, Wang JM. (1999) T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor. Blood, 93 (11): 3885-92. [PMID:10339497]

81. Sun R, Iribarren P, Zhang N, Zhou Y, Gong W, Cho EH, Lockett S, Chertov O, Bednar F, Rogers TJ, Oppenheim JJ, Wang JM. (2004) Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor. J Immunology, 173: 428-436. [PMID:15210802]

82. Takenawa T, Ishitoya J, Homma Y, Kato M, Nagai Y. (1985) Role of enhanced inositol phospholipid metabolism in neutrophil activation. Biochem Pharmacol, 34 (11): 1931-5. [PMID:2988563]

83. Unitt J, Fagura M, Phillips T, King S, Perry M, Morley A, MacDonald C, Weaver R, Christie J, Barber S et al.. (2011) Discovery of small molecule human FPR1 receptor antagonists. Bioorg Med Chem Lett, 21 (10): 2991-7. [PMID:21486695]

84. Walther A, Riehemann K, Gerke V. (2000) A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Mol Cell, 5 (5): 831-40. [PMID:10882119]

85. Wenzel-Seifert K, Grünbaum L, Seifert R. (1991) Differential inhibition of human neutrophil activation by cyclosporins A, D, and H. Cyclosporin H is a potent and effective inhibitor of formyl peptide-induced superoxide formation. J Immunol, 147 (6): 1940-6. [PMID:1653806]

86. Wenzel-Seifert K, Seifert R. (1993) Cyclosporin H is a potent and selective formyl peptide receptor antagonist. Comparison with N-t-butoxycarbonyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L- leucyl-L-phenylalanine and cyclosporins A, B, C, D, and E. J Immunol, 150 (10): 4591-9. [PMID:8387097]

87. Williams LT, Snyderman R, Pike MC, Lefkowitz RJ. (1977) Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc Natl Acad Sci USA, 74 (3): 1204-8. [PMID:265563]

88. Yamamoto Y, Kanazawa T, Shimamura M, Ueki M, Hazato T. (1997) Inhibitory effects of spinorphin, a novel endogenous regulator, on chemotaxis, O2- generation, and exocytosis by N-formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils. Biochem Pharmacol, 54 (6): 695-701. [PMID:9310346]

89. Yan P, Nanamori M, Sun M, Zhou C, Cheng N, Li N, Zheng W, Xiao L, Xie X, Ye RD et al.. (2006) The immunosuppressant cyclosporin A antagonizes human formyl peptide receptor through inhibition of cognate ligand binding. J Immunol, 177 (10): 7050-8. [PMID:17082621]

90. Young SM, Bologa C, Prossnitz ER, Oprea TI, Sklar LA, Edwards BS. (2005) High-throughput screening with HyperCyt flow cytometry to detect small molecule formylpeptide receptor ligands. J Biomol Screen, 10 (4): 374-82. [PMID:15964939]

91. Zigmond SH. (1977) Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors. J Cell Biol, 75 (2 Pt 1): 606-16. [PMID:264125]


Show »

How to cite this page