Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCL9OC5)

• DOT Name: Substance-P receptor (TACR1)
• Synonyms: SPR; NK-1 receptor; NK-1R; Tachykinin receptor 1
• Gene Name: TACR1
• UniProt ID: NK1R_HUMAN
• PDB ID: 2KS9; 2KSA; 2KSB; 6E59; 6HLL; 6HLO; 6HLP; 7P00; 7P02; 7RMG; 7RMH; 7RMI; 8U26
• Pfam ID: PF00001
• Sequence:
  MDNVLPVDSDLSPNISTNTSEPNQFVQPAWQIVLWAAAYTVIVVTSVVGNVVVMWIILAH
  KRMRTVTNYFLVNLAFAEASMAAFNTVVNFTYAVHNEWYYGLFYCKFHNFFPIAAVFASI
  YSMTAVAFDRYMAIIHPLQPRLSATATKVVICVIWVLALLLAFPQGYYSTTETMPSRVVC
  MIEWPEHPNKIYEKVYHICVTVLIYFLPLLVIGYAYTVVGITLWASEIPGDSSDRYHEQV
  SAKRKVVKMMIVVVCTFAICWLPFHIFFLLPYINPDLYLKKFIQQVYLAIMWLAMSSTMY
  NPIIYCCLNDRFRLGFKHAFRCCPFISAGDYEGLEMKSTRYLQTQGSVYKVSRLETTIST
  VVGAHEEEPEDGPKATPSSLDLTSNCSSRSDSKTMTESFSFSSNVLS
• Function: This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Tachykinin receptors bind tachykinins (R-HSA-380095)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Substance-P receptor (TACR1).	[1]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the activity of Substance-P receptor (TACR1).	[2]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Substance-P receptor (TACR1).	[5]
Taurine	DMVW7N3	Investigative	Taurine decreases the expression of Substance-P receptor (TACR1).	[6]
SU5402	DM9JON3	Investigative	SU5402 decreases the expression of Substance-P receptor (TACR1).	[7]

2 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 Substance-P receptor (TACR1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Substance-P receptor (TACR1).	[4]

References

• [1] Valproic acid inhibits substance P-induced activation of protein kinase C epsilon and expression of the substance P receptor. J Neurochem. 2003 Jul;86(1):69-76. doi: 10.1046/j.1471-4159.2003.01802.x.
• [2] Characterization of the potent, selective Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one, in cellular and in vivo models of pulmonary oxidative stress. J Pharmacol Exp Ther. 2017 Oct;363(1):114-125.
• [3] 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.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [6] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.
• [7] Regulation of neurokinin-1 receptor messenger RNA expression in synovial fibroblasts of patients with rheumatoid arthritis. Neuropeptides. 2005 Oct;39(5):467-74. doi: 10.1016/j.npep.2005.07.005. Epub 2005 Sep 9.