Target Information

Target General Infomation
Target ID
T51076 (Former ID: TTDI01807)
Target Name
NT-3 growth factor receptor (TrkC)
Synonyms
TrkC tyrosine kinase; Trk-C; TRKC; Neurotrophic tyrosine kinase receptor type 3; NT3 growth factor receptor; GP145TrkC; GP145-TrkC
Gene Name
NTRK3
Target Type
Successful target
 [1]
Disease [+] 1 Target-related Diseases +
1 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Function
Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. Receptor tyrosine kinase involved in nervous system and probably heart development.
BioChemical Class
Kinase
UniProt ID
NTRK3_HUMAN
EC Number
EC 2.7.10.1
Sequence
MDVSLCPAKCSFWRIFLLGSVWLDYVGSVLACPANCVCSKTEINCRRPDDGNLFPLLEGQ
DSGNSNGNASINITDISRNITSIHIENWRSLHTLNAVDMELYTGLQKLTIKNSGLRSIQP
RAFAKNPHLRYINLSSNRLTTLSWQLFQTLSLRELQLEQNFFNCSCDIRWMQLWQEQGEA
KLNSQNLYCINADGSQLPLFRMNISQCDLPEISVSHVNLTVREGDNAVITCNGSGSPLPD
VDWIVTGLQSINTHQTNLNWTNVHAINLTLVNVTSEDNGFTLTCIAENVVGMSNASVALT
VYYPPRVVSLEEPELRLEHCIEFVVRGNPPPTLHWLHNGQPLRESKIIHVEYYQEGEISE
GCLLFNKPTHYNNGNYTLIAKNPLGTANQTINGHFLKEPFPESTDNFILFDEVSPTPPIT
VTHKPEEDTFGVSIAVGLAAFACVLLVVLFVMINKYGRRSKFGMKGPVAVISGEEDSASP
LHHINHGITTPSSLDAGPDTVVIGMTRIPVIENPQYFRQGHNCHKPDTYVQHIKRRDIVL
KRELGEGAFGKVFLAECYNLSPTKDKMLVAVKALKDPTLAARKDFQREAELLTNLQHEHI
VKFYGVCGDGDPLIMVFEYMKHGDLNKFLRAHGPDAMILVDGQPRQAKGELGLSQMLHIA
SQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSRDVYSTDYYRLFNPSGNDF
CIWCEVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVI
ECITQGRVLERPRVCPKEVYDVMLGCWQREPQQRLNIKEIYKILHALGKATPIYLDILG
Drugs and Modes of Action
Approved Drug(s) [+] 2 Approved Drugs +
1 Larotrectinib Drug Info Approved Solid tumour/cancer [1]
2 LOXO-101 Drug Info Approved Solid tumour/cancer [2]
Clinical Trial Drug(s) [+] 3 Clinical Trial Drugs +
1 RXDX 101 Drug Info Phase 2 Colorectal cancer [3]
2 MK-2461 Drug Info Phase 1/2 Alzheimer disease [4]
3 Altiratinib Drug Info Phase 1 Solid tumour/cancer [5]
Patented Agent(s) [+] 5 Patented Agents +
1 3-amino-5-benzyl-substituted indazole derivative 1 Drug Info Patented Pruritus [6]
2 Azaindazole amide derivative 1 Drug Info Patented Pruritus [6]
3 PMID28270021-Compound-WO2015042088Example4 Drug Info Patented Pruritus [6]
4 PMID28270021-Compound-WO2016054807Example1 Drug Info Patented Pruritus [6]
5 Pyrrolo[2,3-d]pyrimidine derivative 4 Drug Info Patented Pruritus [6]
Discontinued Drug(s) [+] 1 Discontinued Drugs +
1 CEP-2563 Drug Info Discontinued in Phase 1 Solid tumour/cancer [7]
Mode of Action [+] 2 Modes of Action +
Inhibitor [+] 20 Inhibitor drugs +
1 Larotrectinib Drug Info [1]
2 LOXO-101 Drug Info [8]
3 RXDX 101 Drug Info [8]
4 MK-2461 Drug Info [4]
5 Altiratinib Drug Info [9]
6 3-amino-5-benzyl-substituted indazole derivative 1 Drug Info [6]
7 Azaindazole amide derivative 1 Drug Info [6]
8 Cyclopenta[d]pyrimidine derivative 1 Drug Info [9]
9 PMID28270010-Compound-Figure24-b Drug Info [9]
10 PMID28270010-Compound-Figure5-1 Drug Info [9]
11 PMID28270010-Compound-Figure5-2 Drug Info [9]
12 PMID28270010-Compound-Figure5-3 Drug Info [9]
13 PMID28270021-Compound-WO2015042088Example4 Drug Info [6]
14 PMID28270021-Compound-WO2016054807Example1 Drug Info [6]
15 Pyrrolo[2,3-d]pyrimidine derivative 4 Drug Info [6]
16 AZD1332 Drug Info [11]
17 GNF-5837 Drug Info [12]
18 JNJ-28312141 Drug Info [13]
19 PMID21493067C1d Drug Info [14]
20 PMID24900538C2c Drug Info [15]
Modulator [+] 1 Modulator drugs +
1 CEP-2563 Drug Info [10]
Target Regulators
Target-regulating microRNAs
Target-regulating microRNAs Info 
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Expression Profile Info 
Drug Resistance
 Mutation (DRM)
Drug Resistance Mutation Info 
Target Affiliated Biological Pathways
Reactome [+] 3 Reactome Pathways +
1 ARMS-mediated activation
2 NGF-independant TRKA activation
3 PI3K/AKT activation
WikiPathways [+] 4 WikiPathways +
1 MAPK Signaling Pathway
2 BDNF signaling pathway
3 Integrated Pancreatic Cancer Pathway
4 NGF signalling via TRKA from the plasma membrane
References
REF 1 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
REF 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 4 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
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 800040094)
REF 6 Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part II.Expert Opin Ther Pat. 2017 Jul;27(7):831-849.
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 800007988)
REF 8 ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. 2014 Jul;12(7):429-39.
REF 9 Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
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.
REF 11 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: 1817).
REF 12 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 13 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 14 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 15 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.

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