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.
Click to Show/Hide
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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 | |||||
|---|---|---|---|---|---|---|
| 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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