Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOJ1NF)

• DTT Name: FMLP-related receptor I (FPR2)
• Synonyms: RFP; Lipoxin A4 receptor; LXA4 receptor; HM63; G-protein-coupled receptor FPR-Like-1; Formyl peptide receptor-like 1; FPRL1; FPR2; FMLP-R-I
• Gene Name: FPR2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: FPR2_HUMAN
• TTD ID: T97917
• Sequence:
  METNFSTPLNEYEEVSYESAGYTVLRILPLVVLGVTFVLGVLGNGLVIWVAGFRMTRTVT
  TICYLNLALADFSFTATLPFLIVSMAMGEKWPFGWFLCKLIHIVVDINLFGSVFLIGFIA
  LDRCICVLHPVWAQNHRTVSLAMKVIVGPWILALVLTLPVFLFLTTVTIPNGDTYCTFNF
  ASWGGTPEERLKVAITMLTARGIIRFVIGFSLPMSIVAICYGLIAAKIHKKGMIKSSRPL
  RVLTAVVASFFICWFPFQLVALLGTVWLKEMLFYGKYKIIDILVNPTSSLAFFNSCLNPM
  LYVFVGQDFRERLIHSLPTSLERALSEDSAPTNDTAANSASPPAETELQAM
• Function: Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophils chemotactic factors. Binding of FMLP to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The activation of LXA4R could result in an anti-inflammatory outcome counteracting the actions of proinflammatory signals such as LTB4 (leukotrieneB4).
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Neutrophil extracellular trap formation (hsa04613)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
humanin	DMUAPNF	Alzheimer disease	8A20	Preclinical	[2]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AG-26	DMMFQR2	Discovery agent	N.A.	Investigative	[3]
aspirin triggered lipoxin A4	DMLBSNP	Discovery agent	N.A.	Investigative	[4]
aspirin-triggered resolvin D1	DMOP941	Discovery agent	N.A.	Investigative	[1]
ATLa2	DMA632U	Discovery agent	N.A.	Investigative	[5]
fMet-Leu-Phe	DMQ391A	N. A.	N. A.	Investigative	[6]
LXA4	DMGSVL0	Discovery agent	N.A.	Investigative	[7]
PMID22607879CR-(-)-5f	DM7OJ5Q	Discovery agent	N.A.	Investigative	[8]
PMID23788657C1754-31	DM2FDJN	Discovery agent	N.A.	Investigative	[9]
pyrazolone, 1	DMLFQKU	Discovery agent	N.A.	Investigative	[10]
quin-C1	DMVQYWS	Discovery agent	N.A.	Investigative	[11]
quin-C7	DM1CYWB	Discovery agent	N.A.	Investigative	[12]
RvD1-ME	DM8EZTM	Discovery agent	N.A.	Investigative	[1]
[3H]resolvin D1	DMFT0HU	Discovery agent	N.A.	Investigative	[7]

References

• [1] Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs. Am J Pathol. 2012 May;180(5):2018-27.
• [2] N-Formylated humanin activates both formyl peptide receptor-like 1 and 2. Biochem Biophys Res Commun. 2004 Nov 5;324(1):255-61.
• [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] 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: 223).
• [5] Novel 3-oxa lipoxin A4 analogues with enhanced chemical and metabolic stability have anti-inflammatory activity in vivo. J Med Chem. 2004 Apr 8;47(8):2157-65.
• [6] Multiple domains of the N-formyl peptide receptor are required for high-affinity ligand binding. Construction and analysis of chimeric N-formyl peptide receptors. J Biol Chem. 1993 Aug 25;268(24):18167-75.
• [7] Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1660-5.
• [8] 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.
• [9] Selective agonists and antagonists of formylpeptide receptors: duplex flow cytometry and mixture-based positional scanning libraries. Mol Pharmacol. 2013 Sep;84(3):314-24.
• [10] Potent hFPRL1 (ALXR) agonists as potential anti-inflammatory agents. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3713-8.
• [11] A novel nonpeptide ligand for formyl peptide receptor-like 1. Mol Pharmacol. 2004 Nov;66(5):1213-22.
• [12] Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1. Mol Pharmacol. 2007 Oct;72(4):976-83.