Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3SRH4H)

• DOT Name: Leukotriene B4 receptor 1 (LTB4R)
• Synonyms: LTB4-R 1; LTB4-R1; Chemoattractant receptor-like 1; G-protein coupled receptor 16; P2Y purinoceptor 7; P2Y7
• Gene Name: LTB4R
• UniProt ID: LT4R1_HUMAN
• PDB ID: 7K15; 7VKT
• Pfam ID: PF00001
• Sequence:
  MNTTSSAAPPSLGVEFISLLAIILLSVALAVGLPGNSFVVWSILKRMQKRSVTALMVLNL
  ALADLAVLLTAPFFLHFLAQGTWSFGLAGCRLCHYVCGVSMYASVLLITAMSLDRSLAVA
  RPFVSQKLRTKAMARRVLAGIWVLSFLLATPVLAYRTVVPWKTNMSLCFPRYPSEGHRAF
  HLIFEAVTGFLLPFLAVVASYSDIGRRLQARRFRRSRRTGRLVVLIILTFAAFWLPYHVV
  NLAEAGRALAGQAAGLGLVGKRLSLARNVLIALAFLSSSVNPVLYACAGGGLLRSAGVGF
  VAKLLEGTGSEASSTRRGGSLGQTARSGPAALEPGPSESLTASSPLKLNELN
• Function: Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y receptor involved in the regulation of cardiac muscle contraction through modulation of L-type calcium currents. Is a receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response.
• Tissue Specificity: Expressed at highest levels in heart, skeletal muscle and at lower levels in brain and liver. High level of expression in lymphoid tissues.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Leukotriene receptors (R-HSA-391906)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukotriene B4 receptor 1 (LTB4R).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leukotriene B4 receptor 1 (LTB4R).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Leukotriene B4 receptor 1 (LTB4R).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Leukotriene B4 receptor 1 (LTB4R).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Leukotriene B4 receptor 1 (LTB4R).	[5]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Leukotriene B4 receptor 1 (LTB4R).	[6]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Leukotriene B4 receptor 1 (LTB4R).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Leukotriene B4 receptor 1 (LTB4R).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Leukotriene B4 receptor 1 (LTB4R).	[10]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of Leukotriene B4 receptor 1 (LTB4R).	[11]

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 increases the methylation of Leukotriene B4 receptor 1 (LTB4R).	[9]

References

• [1] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [7] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [8] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009 Feb 12;177(3):173-80. doi: 10.1016/j.cbi.2008.10.051. Epub 2008 Nov 6.