Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Neurotensin receptor type 1 (NTSR1)
• Synonyms: NTSR1; NTRH; NTR1; NTR subtype 1; NT-R1; NT-R-1; High-affinity levocabastine-insensitive neurotensin receptor
• Gene Name: NTSR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NTR1_HUMAN
• TTD ID: T02728
• 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.
• KEGG Pathway:
  Calcium signaling 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 DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meclinertant	DMBIO6E	Inflammatory bowel disease	DD72	Phase 2/3	[1]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABS-212	DMZ52P6	Pain	MG30-MG3Z	Terminated	[2]
CGX-1160	DMADYF7	Acute or chronic pain	MG30-MG31	Terminated	[3]

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[4]
Demotensin 1	DMRICV6	Discovery agent	N.A.	Investigative	[5]
Demotensin 2	DMW2GA4	Discovery agent	N.A.	Investigative	[5]
Demotensin 3	DMS0V84	Discovery agent	N.A.	Investigative	[5]
Demotensin 4	DMB2HXM	Discovery agent	N.A.	Investigative	[5]
EISAI-1	DM03X7D	Discovery agent	N.A.	Investigative	[6]
H-Arg-Arg-Pro-Tyr-Ile-Aac-OH	DMENVKA	Discovery agent	N.A.	Investigative	[7]
H-Arg-Arg-Pro-Tyr-Ile-N-Me-Leu-OH	DM4FKR1	Discovery agent	N.A.	Investigative	[7]
H-Arg-Arg-Pro-Tyr-N-Me-Ile-Leu-OH	DM107RT	Discovery agent	N.A.	Investigative	[7]
H-Arg-N-Me-Arg-Pro-Tyr-Ile-Leu-OH	DMSXLKJ	Discovery agent	N.A.	Investigative	[7]
HBN-2	DM5VDU2	Neurological disorder	6B60	Investigative	[8]
JMV449	DME9GF8	Discovery agent	N.A.	Investigative	[6]
JMV458	DMC1ARG	Discovery agent	N.A.	Investigative	[9]
NEUROTENSIN	DM27WCE	Discovery agent	N.A.	Investigative	[10]
Neurotensin(8-13)	DMOBU62	N. A.	N. A.	Investigative	[11]
NT-69-L	DMUHZ2V	Alcohol dependence	6C40.2	Investigative	[8]
SR142948A	DMMXU6R	Discovery agent	N.A.	Investigative	[12]
SR48527	DMUHQS9	Discovery agent	N.A.	Investigative	[13]
[3H]meclinertant	DMEX6GT	Discovery agent	N.A.	Investigative	[13]

References

• [1] Neurotensin inversely modulates maternal aggression. Neuroscience. 2009 Feb 18;158(4):1215-23.
• [2] Identification and functional characterization of a stable, centrally active derivative of the neurotensin (8-13) fragment as a potential first-in-class analgesic. J Med Chem. 2010 Jun 24;53(12):4623-32.
• [3] Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem. 2008 Aug;8(6):603-17.
• [4] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [5] Toward stable N4-modified neurotensins for NTS1-receptor-targeted tumor imaging with 99mTc. J Med Chem. 2006 Jul 27;49(15):4767-76.
• [6] Differential involvement of intracellular domains of the rat NTS1 neurotensin receptor in coupling to G proteins: a molecular basis for agonist-directed trafficking of receptor stimulus. Mol Pharmacol. 2003 Aug;64(2):421-9.
• [7] Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling of neurotensi... Bioorg Med Chem. 2008 Oct 15;16(20):9359-68.
• [8] 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: 309).
• [9] Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2. Mol Pharmacol. 2001 Dec;60(6):1392-8.
• [10] Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
• [11] Comparison of N-terminal modifications on neurotensin(8-13) analogues correlates peptide stability but not binding affinity with in vivo efficacy. J Med Chem. 2009 Apr 9;52(7):1803-13.
• [12] Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist. J Pharmacol Exp Ther. 1997 Feb;280(2):802-12.
• [13] [3H]SR 48692, the first nonpeptide neurotensin antagonist radioligand: characterization of binding properties and evidence for distinct agonist and antagonist binding domains on the rat neurotensin receptor. Mol Pharmacol. 1995 May;47(5):1050-6.