Target General Infomation
Target ID
T51076
Former ID
TTDI01807
Target Name
Trk receptor
Gene Name
NTRK3
Synonyms
GP145TrkC; NT3 growth factor receptor; Neurotrophic tyrosine kinase receptor type 3; TrkC; TrkC tyrosine kinase; NTRK3
Target Type
Clinical Trial
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.
BioChemical Class
Kinase
UniProt ID
EC Number
EC 2.7.10.1
Sequence
MDVSLCPAKCSFWRIFLLGSVWLDYVGSVLACPANCVCSKTEINCRRPDDGNLFPLLEGQ
DSGNSNGNASINITDISRNITSIHIENWRSLHTLNAVDMELYTGLQKLTIKNSGLRSIQP
RAFAKNPHLRYINLSSNRLTTLSWQLFQTLSLRELQLEQNFFNCSCDIRWMQLWQEQGEA
KLNSQNLYCINADGSQLPLFRMNISQCDLPEISVSHVNLTVREGDNAVITCNGSGSPLPD
VDWIVTGLQSINTHQTNLNWTNVHAINLTLVNVTSEDNGFTLTCIAENVVGMSNASVALT
VYYPPRVVSLEEPELRLEHCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEYYQEGEISE
GCLLFNKPTHYNNGNYTLIAKNPLGTANQTINGHFLKEPFPESTDNFILFDEVSPTPPIT
VTHKPEEDTFGVSIAVGLAAFACVLLVVLFVMINKYGRRSKFGMKGPVAVISGEEDSASP
LHHINHGITTPSSLDAGPDTVVIGMTRIPVIENPQYFRQGHNCHKPDTYVQHIKRRDIVL
KRELGEGAFGKVFLAECYNLSPTKDKMLVAVKALKDPTLAARKDFQREAELLTNLQHEHI
VKFYGVCGDGDPLIMVFEYMKHGDLNKFLRAHGPDAMILVDGQPRQAKGELGLSQMLHIA
SQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSRDVYSTDYYRLFNPSGNDF
CIWCEVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVI
ECITQGRVLERPRVCPKEVYDVMLGCWQREPQQRLNIKEIYKILHALGKATPIYLDILG
Structure
1WWC; 3V5Q; 1HE7; 1SHC; 1WWA; 1WWW; 2IFG; 4AOJ; 4CRP; 4F0I; 4GT5; 4PMM; 4PMP; 4PMS; 4PMT
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 1MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
REF 2ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. 2014 Jul;12(7):429-39.
REF 3ClinicalTrials.gov (NCT02122913) Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Adult Solid Tumors. U.S. National Institutes of Health.
REF 4Trusted, 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 6In 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 7Discovery 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 8Discovery 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 9JNJ-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 10Phase 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.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.