Target Information
| Target General Information | Top | |||||
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| Target ID |
T02728
(Former ID: TTDC00144)
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| Target Name |
Neurotensin receptor type 1 (NTSR1)
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| Synonyms |
NTSR1; NTRH; NTR1; NTR subtype 1; NT-R1; NT-R-1; High-affinity levocabastine-insensitive neurotensin receptor
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| Gene Name |
NTSR1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Indeterminate colitis [ICD-11: DD72] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MRLNSSAPGTPGTPAADPFQRAQAGLEEALLAPGFGNASGNASERVLAAPSSELDVNTDI
YSKVLVTAVYLALFVVGTVGNTVTAFTLARKKSLQSLQSTVHYHLGSLALSDLLTLLLAM PVELYNFIWVHHPWAFGDAGCRGYYFLRDACTYATALNVASLSVERYLAICHPFKAKTLM SRSRTKKFISAIWLASALLAVPMLFTMGEQNRSADGQHAGGLVCTPTIHTATVKVVIQVN TFMSFIFPMVVISVLNTIIANKLTVMVRQAAEQGQVCTVGGEHSTFSMAIEPGRVQALRH GVRVLRAVVIAFVVCWLPYHVRRLMFCYISDEQWTPFLYDFYHYFYMVTNALFYVSSTIN PILYNLVSANFRHIFLATLACLCPVWRRRRKRPAFSRKADSVSSNHTLSSNATRETLY Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Meclinertant | Drug Info | Phase 2/3 | Inflammatory bowel disease | [2], [3] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | ABS-212 | Drug Info | Terminated | Pain | [4], [5] | |
| 2 | CGX-1160 | Drug Info | Terminated | Acute or chronic pain | [6], [7] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Antagonist | [+] 4 Antagonist drugs | + | ||||
| 1 | Meclinertant | Drug Info | [1], [8], [9] | |||
| 2 | SR142948A | Drug Info | [21] | |||
| 3 | SR48527 | Drug Info | [22] | |||
| 4 | [3H]meclinertant | Drug Info | [22] | |||
| Agonist | [+] 5 Agonist drugs | + | ||||
| 1 | ABS-212 | Drug Info | [10] | |||
| 2 | CGX-1160 | Drug Info | [11], [12] | |||
| 3 | EISAI-1 | Drug Info | [15] | |||
| 4 | JMV449 | Drug Info | [15] | |||
| 5 | JMV458 | Drug Info | [18] | |||
| Inhibitor | [+] 11 Inhibitor drugs | + | ||||
| 1 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [13] | |||
| 2 | Demotensin 1 | Drug Info | [14] | |||
| 3 | Demotensin 2 | Drug Info | [14] | |||
| 4 | Demotensin 3 | Drug Info | [14] | |||
| 5 | Demotensin 4 | Drug Info | [14] | |||
| 6 | H-Arg-Arg-Pro-Tyr-Ile-Aac-OH | Drug Info | [16] | |||
| 7 | H-Arg-Arg-Pro-Tyr-Ile-N-Me-Leu-OH | Drug Info | [16] | |||
| 8 | H-Arg-Arg-Pro-Tyr-N-Me-Ile-Leu-OH | Drug Info | [16] | |||
| 9 | H-Arg-N-Me-Arg-Pro-Tyr-Ile-Leu-OH | Drug Info | [16] | |||
| 10 | NEUROTENSIN | Drug Info | [19] | |||
| 11 | Neurotensin(8-13) | Drug Info | [20] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | HBN-2 | Drug Info | [17] | |||
| 2 | NT-69-L | Drug Info | [17] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 3 | Peptide GPCRs | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| 6 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Neurotensin inversely modulates maternal aggression. Neuroscience. 2009 Feb 18;158(4):1215-23. | |||||
| REF 2 | 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. (Ligand id: 1582). | |||||
| REF 3 | ClinicalTrials.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 4 | 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. (Ligand id: 5307). | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026502) | |||||
| REF 6 | 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. (Ligand id: 1575). | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012898) | |||||
| REF 8 | Stimulation by neurotensin of dopamine and 5-hydroxytryptamine (5-HT) release from rat prefrontal cortex: possible role of NTR1 receptors in neurop... Neurochem Int. 2008 Dec;53(6-8):355-61. | |||||
| REF 9 | High-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. | |||||
| REF 10 | 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. | |||||
| REF 11 | Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem. 2008 Aug;8(6):603-17. | |||||
| REF 12 | The 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 13 | 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. | |||||
| REF 14 | Toward stable N4-modified neurotensins for NTS1-receptor-targeted tumor imaging with 99mTc. J Med Chem. 2006 Jul 27;49(15):4767-76. | |||||
| REF 15 | 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. | |||||
| REF 16 | 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. | |||||
| REF 17 | 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). | |||||
| REF 18 | Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2. Mol Pharmacol. 2001 Dec;60(6):1392-8. | |||||
| REF 19 | 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. | |||||
| REF 20 | 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. | |||||
| REF 21 | Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist. J Pharmacol Exp Ther. 1997 Feb;280(2):802-12. | |||||
| REF 22 | [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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