Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTJUTE3)

• DOT Name: Neurotensin receptor type 1 (NTSR1)
• Synonyms: NT-R-1; NTR1; High-affinity levocabastine-insensitive neurotensin receptor; NTRH
• Gene Name: NTSR1
• UniProt ID: NTR1_HUMAN
• PDB ID: 2LYW; 6OS9; 6OSA; 6PWC; 6UP7; 7UL2; 8JPB; 8JPC; 8JPF
• Pfam ID: PF00001
• Sequence:
  MRLNSSAPGTPGTPAADPFQRAQAGLEEALLAPGFGNASGNASERVLAAPSSELDVNTDI
  YSKVLVTAVYLALFVVGTVGNTVTAFTLARKKSLQSLQSTVHYHLGSLALSDLLTLLLAM
  PVELYNFIWVHHPWAFGDAGCRGYYFLRDACTYATALNVASLSVERYLAICHPFKAKTLM
  SRSRTKKFISAIWLASALLAVPMLFTMGEQNRSADGQHAGGLVCTPTIHTATVKVVIQVN
  TFMSFIFPMVVISVLNTIIANKLTVMVRQAAEQGQVCTVGGEHSTFSMAIEPGRVQALRH
  GVRVLRAVVIAFVVCWLPYHVRRLMFCYISDEQWTPFLYDFYHYFYMVTNALFYVSSTIN
  PILYNLVSANFRHIFLATLACLCPVWRRRRKRPAFSRKADSVSSNHTLSSNATRETLY
• Function: G-protein coupled receptor for the tridecapeptide neurotensin (NTS). Signaling is effected via G proteins that activate a phosphatidylinositol-calcium second messenger system. Signaling leads to the activation of downstream MAP kinases and protects cells against apoptosis.
• Tissue Specificity: Expressed in prostate (at protein level). Detected in colon and peripheral blood mononuclear cells. Detected at very low levels in brain.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Neurotensin receptor type 1 (NTSR1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neurotensin receptor type 1 (NTSR1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neurotensin receptor type 1 (NTSR1).	[2]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Neurotensin receptor type 1 (NTSR1).	[3]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Neurotensin receptor type 1 (NTSR1).	[4]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Neurotensin receptor type 1 (NTSR1).	[5]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Neurotensin receptor type 1 (NTSR1).	[7]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
NEUROTENSIN	DM27WCE	Investigative	NEUROTENSIN affects the binding of Neurotensin receptor type 1 (NTSR1).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [3] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [4] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [5] Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. J Nutr. 2006 Jan;136(1):75-82.
• [6] 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.
• [7] Roles of acyl-CoA synthetase long-chain family member 5 and colony stimulating factor 2 in inhibition of palmitic or stearic acids in lung cancer cell proliferation and metabolism. Cell Biol Toxicol. 2021 Feb;37(1):15-34. doi: 10.1007/s10565-020-09520-w. Epub 2020 Apr 28.
• [8] NT79: A novel neurotensin analog with selective behavioral effects. Brain Res. 2010 Jan 13;1308:35-46. doi: 10.1016/j.brainres.2009.10.050. Epub 2009 Oct 27.