Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T51076
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| Former ID |
TTDI01807
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| Target Name |
Trk receptor
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| Gene Name |
NTRK3
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| Synonyms |
GP145TrkC; NT3 growth factor receptor; Neurotrophic tyrosine kinase receptor type 3; TrkC; TrkC tyrosine kinase; NTRK3
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| Target Type |
Clinical Trial
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| Disease | Alzheimer disease [ICD9: 331; ICD10: G30] | ||||
| Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
| Function |
Receptor for neurotrophin-3 (NT-3). This is a tyrosine- protein kinase receptor. Known substrates for the trk receptors are SHC1, PI-3 kinase, and PLCG1. The different isoforms do not have identical signaling properties.
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| BioChemical Class |
Kinase
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| UniProt ID | |||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MDVSLCPAKCSFWRIFLLGSVWLDYVGSVLACPANCVCSKTEINCRRPDDGNLFPLLEGQ
DSGNSNGNASINITDISRNITSIHIENWRSLHTLNAVDMELYTGLQKLTIKNSGLRSIQP RAFAKNPHLRYINLSSNRLTTLSWQLFQTLSLRELQLEQNFFNCSCDIRWMQLWQEQGEA KLNSQNLYCINADGSQLPLFRMNISQCDLPEISVSHVNLTVREGDNAVITCNGSGSPLPD VDWIVTGLQSINTHQTNLNWTNVHAINLTLVNVTSEDNGFTLTCIAENVVGMSNASVALT VYYPPRVVSLEEPELRLEHCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEYYQEGEISE GCLLFNKPTHYNNGNYTLIAKNPLGTANQTINGHFLKEPFPESTDNFILFDEVSPTPPIT VTHKPEEDTFGVSIAVGLAAFACVLLVVLFVMINKYGRRSKFGMKGPVAVISGEEDSASP LHHINHGITTPSSLDAGPDTVVIGMTRIPVIENPQYFRQGHNCHKPDTYVQHIKRRDIVL KRELGEGAFGKVFLAECYNLSPTKDKMLVAVKALKDPTLAARKDFQREAELLTNLQHEHI VKFYGVCGDGDPLIMVFEYMKHGDLNKFLRAHGPDAMILVDGQPRQAKGELGLSQMLHIA SQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSRDVYSTDYYRLFNPSGNDF CIWCEVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVI ECITQGRVLERPRVCPKEVYDVMLGCWQREPQQRLNIKEIYKILHALGKATPIYLDILG |
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| Structure |
1WWC; 3V5Q; 1HE7; 1SHC; 1WWA; 1WWW; 2IFG; 4AOJ; 4CRP; 4F0I; 4GT5; 4PMM; 4PMP; 4PMS; 4PMT
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| Drugs and Mode of Action | |||||
| Drug(s) | MK-2461 | Drug Info | Phase 1/2 | Alzheimer disease | [1] |
| RXDX 101 | Drug Info | Phase 1/2 | Solid tumours | [2] | |
| LOXO-101 | Drug Info | Phase 1 | Solid tumours | [3] | |
| CEP-2563 | Drug Info | Discontinued in Phase 1 | Solid tumours | [4] | |
| Inhibitor | AZD1332 | Drug Info | [5] | ||
| compound 1d | Drug Info | [6] | |||
| compound 2c | Drug Info | [7] | |||
| GNF-5837 | Drug Info | [8] | |||
| JNJ-28312141 | Drug Info | [9] | |||
| LOXO-101 | Drug Info | [2] | |||
| MK-2461 | Drug Info | [1] | |||
| RXDX 101 | Drug Info | [2] | |||
| Modulator | CEP-2563 | Drug Info | [10] | ||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| DRM | DRM Info | ||||
| Pathways | |||||
| Reactome | ARMS-mediated activation | ||||
| NGF-independant TRKA activation | |||||
| PI3K/AKT activation | |||||
| WikiPathways | MAPK Signaling Pathway | ||||
| BDNF signaling pathway | |||||
| Integrated Pancreatic Cancer Pathway | |||||
| NGF signalling via TRKA from the plasma membrane | |||||
| References | |||||
| REF 1 | MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33. | ||||
| REF 2 | ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. 2014 Jul;12(7):429-39. | ||||
| REF 3 | ClinicalTrials.gov (NCT02122913) Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Adult Solid Tumors. U.S. National Institutes of Health. | ||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007988) | ||||
| 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. (Target id: 1817). | ||||
| REF 6 | In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg Med Chem Lett. 2011 May 15;21(10):2958-61. | ||||
| REF 7 | Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9. | ||||
| REF 8 | Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS Med Chem Lett. 2012 Jan 1;3(2):140-5. | ||||
| REF 9 | JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol Cancer Ther. 2009 Nov;8(11):3151-61. | ||||
| REF 10 | Phase I clinical trial of CEP-2563 dihydrochloride, a receptor tyrosine kinase inhibitor, in patients with refractory solid tumors. Invest New Drugs. 2004 Nov;22(4):449-58. | ||||
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