Target Information

Target General Infomation
Target ID
T02728
Former ID
TTDC00144
Target Name
Neurotensin receptor type 1
Gene Name
NTSR1
Synonyms
High-affinity levocabastine-insensitive neurotensin receptor; NT-R-1; NT-R1; NTR subtype 1; NTR1; NTRH; NTSR1
Target Type
Clinical Trial
Disease Acute or chronic pain [ICD9: 338,780; ICD10: R52, G89]
Alcohol use disorders [ICD9: 303; ICD10: F10.2]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T02728
UniProt ID
P30989
Sequence
MRLNSSAPGTPGTPAADPFQRAQAGLEEALLAPGFGNASGNASERVLAAPSSELDVNTDI
YSKVLVTAVYLALFVVGTVGNTVTAFTLARKKSLQSLQSTVHYHLGSLALSDLLTLLLAM
PVELYNFIWVHHPWAFGDAGCRGYYFLRDACTYATALNVASLSVERYLAICHPFKAKTLM
SRSRTKKFISAIWLASALLAVPMLFTMGEQNRSADGQHAGGLVCTPTIHTATVKVVIQVN
TFMSFIFPMVVISVLNTIIANKLTVMVRQAAEQGQVCTVGGEHSTFSMAIEPGRVQALRH
GVRVLRAVVIAFVVCWLPYHVRRLMFCYISDEQWTPFLYDFYHYFYMVTNALFYVSSTIN
PILYNLVSANFRHIFLATLACLCPVWRRRRKRPAFSRKADSVSSNHTLSSNATRETLY
Drugs and Mode of Action
Drug(s) Meclinertant Drug Info Phase 2/3 Inflammatory bowel disease [1], [2]
ABS-212 Drug Info Terminated Pain [3], [4]
CGX-1160 Drug Info Terminated Acute or chronic pain [5], [6]
Inhibitor 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info [7]
Arg-Arg-Pro-Tyr-Ile-Leu-OH Drug Info [8]
Demotensin 1 Drug Info [9]
Demotensin 2 Drug Info [9]
Demotensin 3 Drug Info [9]
Demotensin 4 Drug Info [9]
H-Arg-Arg-Pro-Tyr-Ile-Aac-OH Drug Info [10]
H-Arg-Arg-Pro-Tyr-Ile-N-Me-Leu-OH Drug Info [10]
H-Arg-Arg-Pro-Tyr-N-Me-Ile-Leu-OH Drug Info [10]
H-Arg-N-Me-Arg-Pro-Tyr-Ile-Leu-OH Drug Info [10]
NEUROTENSIN Drug Info [11]
Neurotensin(8-13) Drug Info [12]
Agonist ABS-212 Drug Info [13]
CGX-1160 Drug Info [14], [15]
EISAI-1 Drug Info [16]
JMV449 Drug Info [16]
JMV458 Drug Info [17]
Modulator HBN-2 Drug Info [18]
NT-69-L Drug Info [18]
Antagonist Meclinertant Drug Info [19], [20], [21]
SR142948A Drug Info [22]
SR48527 Drug Info [23]
[3H]meclinertant Drug Info [23]
Pathways
KEGG Pathway Calcium signaling pathway
Neuroactive ligand-receptor interaction
Reactome Peptide ligand-binding receptors
G alpha (q) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
REF 1ClinicalTrials.gov (NCT00290953) Evaluation of the Overall Survival of Meclinertant Versus Placebo After a First Line Chemotherapy With Cisplatin + Etoposide. U.S. National Institutes of Health.
REF 2(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. (Ligand id: 1582).
REF 3(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. (Ligand id: 5307).
REF 4Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026502)
REF 5(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. (Ligand id: 1575).
REF 6Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012898)
REF 7J Med Chem. 2010 Sep 9;53(17):6386-97.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 receptor agonist with unprecedented selectivity and procognitive potential.
REF 8Bioorg Med Chem Lett. 2008 Mar 15;18(6):2013-8. Epub 2008 Feb 2.Peptide backbone modifications on the C-terminal hexapeptide of neurotensin.
REF 9J Med Chem. 2006 Jul 27;49(15):4767-76.Toward stable N4-modified neurotensins for NTS1-receptor-targeted tumor imaging with 99mTc.
REF 10Bioorg Med Chem. 2008 Oct 15;16(20):9359-68. Epub 2008 Aug 27.Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling ofneurotensin receptor 1.
REF 11J Med Chem. 2008 Jul 24;51(14):4150-69. Epub 2008 Jun 28.Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity.
REF 12J Med Chem. 2009 Apr 9;52(7):1803-13.Comparison of N-terminal modifications on neurotensin(8-13) analogues correlates peptide stability but not binding affinity with in vivo efficacy.
REF 13Identification 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.
REF 14The pharmacokinetics of the conopeptide contulakin-G (CGX-1160) after intrathecal administration: an analysis of data from studies in beagles. Anesth Analg. 2007 Jun;104(6):1514-20, table of contents.
REF 15Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem. 2008 Aug;8(6):603-17.
REF 16Differential 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.
REF 17Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2. Mol Pharmacol. 2001 Dec;60(6):1392-8.
REF 18(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).
REF 19High-affinity neurotensin receptor is involved in phosphoinositide turnover increase by inhibition of sodium pump in neonatal rat brain. Neurochem Res. 2008 Nov;33(11):2206-13. Epub 2008 Aug 29.
REF 20Stimulation by neurotensin of dopamine and 5-hydroxytryptamine (5-HT) release from rat prefrontal cortex: possible role of NTR1 receptors in neuropsychiatric disorders. Neurochem Int. 2008 Dec;53(6-8):355-61. Epub 2008 Sep 12.
REF 21Neurotensin inversely modulates maternal aggression. Neuroscience. 2009 Feb 18;158(4):1215-23. Epub 2008 Dec 7.
REF 22Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist. J Pharmacol Exp Ther. 1997 Feb;280(2):802-12.
REF 23[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.

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