Target Information
Target General Information | Top | |||||
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Target ID |
T51076
(Former ID: TTDI01807)
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Target Name |
NT-3 growth factor receptor (TrkC)
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Synonyms |
TrkC tyrosine kinase; Trk-C; TRKC; Neurotrophic tyrosine kinase receptor type 3; NT3 growth factor receptor; GP145TrkC; GP145-TrkC
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Gene Name |
NTRK3
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Non-small cell lung cancer [ICD-11: 2C25] | |||||
2 | 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.
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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 Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | Entrectinib | Drug Info | Approved | Non-small cell lung cancer | [2] | |
2 | Larotrectinib | Drug Info | Approved | Solid tumour/cancer | [3] | |
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | MK-2461 | Drug Info | Phase 1/2 | Alzheimer disease | [4] | |
2 | 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 | [+] 19 Inhibitor drugs | + | ||||
1 | Entrectinib | Drug Info | [2] | |||
2 | Larotrectinib | Drug Info | [1] | |||
3 | MK-2461 | Drug Info | [4] | |||
4 | Altiratinib | Drug Info | [8] | |||
5 | 3-amino-5-benzyl-substituted indazole derivative 1 | Drug Info | [6] | |||
6 | Azaindazole amide derivative 1 | Drug Info | [6] | |||
7 | Cyclopenta[d]pyrimidine derivative 1 | Drug Info | [8] | |||
8 | PMID28270010-Compound-Figure24-b | Drug Info | [8] | |||
9 | PMID28270010-Compound-Figure5-1 | Drug Info | [8] | |||
10 | PMID28270010-Compound-Figure5-2 | Drug Info | [8] | |||
11 | PMID28270010-Compound-Figure5-3 | Drug Info | [8] | |||
12 | PMID28270021-Compound-WO2015042088Example4 | Drug Info | [6] | |||
13 | PMID28270021-Compound-WO2016054807Example1 | Drug Info | [6] | |||
14 | Pyrrolo[2,3-d]pyrimidine derivative 4 | Drug Info | [6] | |||
15 | AZD1332 | Drug Info | [10] | |||
16 | GNF-5837 | Drug Info | [11] | |||
17 | JNJ-28312141 | Drug Info | [12] | |||
18 | PMID21493067C1d | Drug Info | [13] | |||
19 | PMID24900538C2c | Drug Info | [14] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | CEP-2563 | Drug Info | [9] |
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 | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) | ||||||
Drug Resistance Mutation (DRM) |
Target Affiliated Biological Pathways | Top | |||||
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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 | Top | |||||
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REF 1 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019 | |||||
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 | Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751. | |||||
REF 9 | 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 10 | 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 11 | 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 12 | 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 13 | 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 14 | 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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