Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFF9I6W)

• DOT Name: fMet-Leu-Phe receptor (FPR1)
• Synonyms: fMLP receptor; N-formyl peptide receptor; FPR; N-formylpeptide chemoattractant receptor
• Gene Name: FPR1
• Related Disease:
  Susceptibility to localized juvenile periodontitis
  Tourette syndrome
• UniProt ID: FPR1_HUMAN
• PDB ID: 7EUO; 7T6T; 7VFX; 7WVU
• Pfam ID: PF00001
• Sequence:
  METNSSLPTNISGGTPAVSAGYLFLDIITYLVFAVTFVLGVLGNGLVIWVAGFRMTHTVT
  TISYLNLAVADFCFTSTLPFFMVRKAMGGHWPFGWFLCKFVFTIVDINLFGSVFLIALIA
  LDRCVCVLHPVWTQNHRTVSLAKKVIIGPWVMALLLTLPVIIRVTTVPGKTGTVACTFNF
  SPWTNDPKERINVAVAMLTVRGIIRFIIGFSAPMSIVAVSYGLIATKIHKQGLIKSSRPL
  RVLSFVAAAFFLCWSPYQVVALIATVRIRELLQGMYKEIGIAVDVTSALAFFNSCLNPML
  YVFMGQDFRERLIHALPASLERALTEDSTQTSDTATNSTLPSAEVELQAK
• Function: High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors. Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Receptor for TAFA4, mediates its effects on chemoattracting macrophages, promoting phagocytosis and increasing ROS release. Receptor for cathepsin CTSG, leading to increased phagocyte chemotaxis.
• Tissue Specificity: Neutrophils.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Neuroactive ligand-receptor interaction (hsa04080)
  Neutrophil extracellular trap formation (hsa04613)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Formyl peptide receptors bind formyl peptides and many other ligands (R-HSA-444473)
  Interleukin-10 signaling (R-HSA-6783783)
  Neutrophil degranulation (R-HSA-6798695)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Susceptibility to localized juvenile periodontitis	DISCYHW2	Supportive	Autosomal recessive	[1]
Tourette syndrome	DISX9D54	No Known	Unknown	[2]

17 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of fMet-Leu-Phe receptor (FPR1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of fMet-Leu-Phe receptor (FPR1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of fMet-Leu-Phe receptor (FPR1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of fMet-Leu-Phe receptor (FPR1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of fMet-Leu-Phe receptor (FPR1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of fMet-Leu-Phe receptor (FPR1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of fMet-Leu-Phe receptor (FPR1).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of fMet-Leu-Phe receptor (FPR1).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of fMet-Leu-Phe receptor (FPR1).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of fMet-Leu-Phe receptor (FPR1).	[10]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of fMet-Leu-Phe receptor (FPR1).	[12]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of fMet-Leu-Phe receptor (FPR1).	[13]
Masoprocol	DMMVNZ0	Approved	Masoprocol decreases the activity of fMet-Leu-Phe receptor (FPR1).	[14]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of fMet-Leu-Phe receptor (FPR1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of fMet-Leu-Phe receptor (FPR1).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of fMet-Leu-Phe receptor (FPR1).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of fMet-Leu-Phe receptor (FPR1).	[19]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of fMet-Leu-Phe receptor (FPR1).	[16]

References

• [1] Formylpeptide receptor single nucleotide polymorphism 348T>C and its relationship to polymorphonuclear leukocyte chemotaxis in aggressive periodontitis. J Periodontol. 2009 Sep;80(9):1498-505. doi: 10.1902/jop.2009.090103.
• [2] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [10] Regulation of the leucocyte chemoattractant receptor FPR in glioblastoma cells by cell differentiation. Carcinogenesis. 2009 Feb;30(2):348-55. doi: 10.1093/carcin/bgn266. Epub 2008 Nov 26.
• [11] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [12] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [13] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [14] [Effect of nordy on FPR function of malignant human glioma cell line U87]. Yao Xue Xue Bao. 2007 Mar;42(3):257-62.
• [15] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [16] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [17] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [18] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [19] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.