Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5Y4EM)

• DTT Name: N-formyl peptide receptor (FPR1)
• Synonyms: N-formylpeptide chemoattractant receptor; FPR1; FPR
• Gene Name: FPR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: FPR1_HUMAN
• TTD ID: T87831
• Sequence:
  METNSSLPTNISGGTPAVSAGYLFLDIITYLVFAVTFVLGVLGNGLVIWVAGFRMTHTVT
  TISYLNLAVADFCFTSTLPFFMVRKAMGGHWPFGWFLCKFVFTIVDINLFGSVFLIALIA
  LDRCVCVLHPVWTQNHRTVSLAKKVIIGPWVMALLLTLPVIIRVTTVPGKTGTVACTFNF
  SPWTNDPKERINVAVAMLTVRGIIRFIIGFSAPMSIVAVSYGLIATKIHKQGLIKSSRPL
  RVLSFVAAAFFLCWSPYQVVALIATVRIRELLQGMYKEIGIAVDVTSALAFFNSCLNPML
  YVFMGQDFRERLIHALPASLERALTEDSTQTSDTATNSTLPSAEVELQAK
• Function: High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors (PubMed:2161213, PubMed:2176894, PubMed:10514456, PubMed:15153520). Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release (PubMed:2161213, PubMed:1712023, PubMed:15153520). This response is mediated via a G-protein that activates a phosphatidylinositol- calcium second messenger system(PubMed:1712023, PubMed:10514456).
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Neuroactive ligand-receptor interaction (hsa04080)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway: G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rebamipide	DM2GHCR	Peptic ulcer	DA61	Phase 3	[1]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3570-0208	DMT80IF	Discovery agent	N.A.	Investigative	[2]
AG-09/1	DMW7H28	Discovery agent	N.A.	Investigative	[3]
AG-11/03	DMZINUY	Discovery agent	N.A.	Investigative	[4]
AG-14	DMVR9G0	Discovery agent	N.A.	Investigative	[5]
BVT173187	DMULZOP	Discovery agent	N.A.	Investigative	[6]
CGEN-855	DM4FMPJ	Inflammation	1A00-CA43.1	Investigative	[7]
diamide 7	DM4EX8Y	Discovery agent	N.A.	Investigative	[8]
fMet-Leu-Phe	DMQ391A	N. A.	N. A.	Investigative	[9]
group E 1682-2106	DMO6IM1	Discovery agent	N.A.	Investigative	[10]
methionine benzimidazole 6	DMEIP6H	Discovery agent	N.A.	Investigative	[8]
PMID22607879CR-(-)-5f	DM7OJ5Q	Discovery agent	N.A.	Investigative	[11]
pyrazolone, 1	DMLFQKU	Discovery agent	N.A.	Investigative	[12]

References

• [1] Rebamipide suppresses formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production by inhibiting fMLP-receptor binding in human neutrophils. J Pharmacol Exp Ther. 2001 Apr;297(1):388-94.
• [2] Discovery of selective probes and antagonists for G-protein-coupled receptors FPR/FPRL1 and GPR30. Curr Top Med Chem. 2009;9(13):1227-36.
• [3] Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition. Mol Pharmacol. 2010 Feb;77(2):159-70.
• [4] Molecular docking of 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derived small-molecule agonists of human formyl peptide receptor 1. J Mol Model. 2012 Jun;18(6):2831-43.
• [5] High-throughput screening for small-molecule activators of neutrophils: identification of novel N-formyl peptide receptor agonists. Mol Pharmacol. 2007 Apr;71(4):1061-74.
• [6] A non-peptide receptor inhibitor with selectivity for one of the neutrophil formyl peptide receptors, FPR 1. Biochem Pharmacol. 2012 Jun 15;83(12):1655-62.
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 222).
• [8] Discovery of small molecule human FPR1 receptor antagonists. Bioorg Med Chem Lett. 2011 May 15;21(10):2991-7.
• [9] Further studies on the structural requirements for synthetic peptide chemoattractants. Biochemistry. 1980 May 27;19(11):2404-10.
• [10] Integration of virtual screening with high-throughput flow cytometry to identify novel small molecule formylpeptide receptor antagonists. Mol Pharmacol. 2005 Nov;68(5):1301-10.
• [11] 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. 2012 Jun 15;20(12):3781-92.
• [12] Functional characterization of three mouse formyl peptide receptors. Mol Pharmacol. 2013 Feb;83(2):389-98.