Target Information

Target General Infomation
Target ID
T07173
Former ID
TTDC00318
Target Name
Neurotrophic tyrosine kinase receptor 1
Gene Name
NTRK1
Synonyms
NGF-trk receptor type A; P140-TrkA; TRK1 transforming tyrosinekinase protein; Trk-A; NTRK1
Target Type
Clinical Trial
Disease Advanced solid malignancies [ICD9: 140-199, 140-239, 210-229; ICD10: D10-D36, D3A]
Alzheimer disease [ICD9: 331; ICD10: G30]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Psoriasis [ICD9: 696; ICD10: L40]
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Required for high-affinitybinding to nerve growth factor (ngf), neurotrophin-3 and neurotrophin-4/5 but not brain- derived neurotrophic factor (bdnf). Known substrates for the trk receptors are shc, pi-3 kinase, and plc-gamma-1.
BioChemical Class
Kinase
Target Validation
T07173
UniProt ID
P04629
EC Number
EC 2.7.10.1
Sequence
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLH
HLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRL
NLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ
GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMK
SGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWC
IPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT
LLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSV
AVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTE
GKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKML
VAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRF
LRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQ
GLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEI
FTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHAR
LQALAQAPPVYLDVLG
Structure
1HE7; 1SHC; 1WWA; 1WWW; 2IFG; 4AOJ; 4CRP; 4F0I; 4GT5; 4PMM; 4PMP; 4PMS; 4PMT
Drugs and Mode of Action
Drug(s) MIM-D3 Drug Info Phase 3 Alzheimer disease [524465]
CT 327 Drug Info Phase 2 Psoriasis [524232]
RXDX 101 Drug Info Phase 1/2 Solid tumours [532994]
DS-6051 Drug Info Phase 1 Solid tumours [524973]
LOXO-101 Drug Info Phase 1 Solid tumours [524734]
PLX7486 Drug Info Phase 1 Pancreatic cancer [549504]
FX-007 Drug Info Preclinical Pain [549432]
AZD6918 Drug Info Discontinued in Phase 1 Advanced solid malignancies [548789]
Inhibitor AZD6918 Drug Info [550288]
CEP-5104 Drug Info [529647]
CEP-6331 Drug Info [529647]
CT 327 Drug Info [525414]
DS-6051 Drug Info [550518]
FX-007 Drug Info [550350]
GW-5074 Drug Info [526991]
K-252a analogue Drug Info [527569]
LOXO-101 Drug Info [551954]
PLX7486 Drug Info [550497]
RXDX 101 Drug Info [543043]
Agonist MIM-D3 Drug Info [544321]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
DRM DRM Info
Pathways
KEGG Pathway MAPK signaling pathway
Endocytosis
Apoptosis
Neurotrophin signaling pathway
Inflammatory mediator regulation of TRP channels
Pathways in cancer
Transcriptional misregulation in cancer
Thyroid cancer
Central carbon metabolism in cancer
NetPath Pathway IL2 Signaling Pathway
Pathway Interaction Database Neurotrophic factor-mediated Trk receptor signaling
Reactome Frs2-mediated activation
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 524232ClinicalTrials.gov (NCT01808157) A Study to Evaluate the Efficacy, Safety and Tolerability of CT327 in Atopic Dermatitis. U.S. National Institutes of Health.
Ref 524465ClinicalTrials.gov (NCT01960010) A Safety and Efficacy Study of MIM-D3 Ophthalmic Solution for the Treatment of Dry Eye. U.S. National Institutes of Health.
Ref 524734ClinicalTrials.gov (NCT02122913) Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Adult Solid Tumors. U.S. National Institutes of Health.
Ref 524973ClinicalTrials.gov (NCT02279433) A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b. U.S. National Institutes of Health.
Ref 532994ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. 2014 Jul;12(7):429-39.
Ref 548789Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028850)
Ref 549432Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037108)
Ref 549504Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038879)
Ref 525414Topical TrkA Kinase Inhibitor CT327 is an Effective, Novel Therapy for the Treatment of Pruritus due to Psoriasis: Results from Experimental Studies, and Efficacy and Safety of CT327 in a Phase 2b Clinical Trial in Patients with Psoriasis. Acta Derm Venereol. 2015 May;95(5):542-8.
Ref 526991Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles.
Ref 527569J Med Chem. 2005 Jun 2;48(11):3776-83.Synthesis, modeling, and in vitro activity of (3'S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3'-sugar alcohol on trkA tyrosine kinase activity.
Ref 529647J Med Chem. 2008 Sep 25;51(18):5680-9. Epub 2008 Aug 21.Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models.
Ref 543043(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. (Ligand id: 8290).
Ref 544321Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye. Clin Ophthalmol. 2013; 7: 1275-1285.
Ref 550288Clinical pipeline report, company report or official report of AstraZeneca (2009).
Ref 550350Preclinical trail of FX007 for treating osteoarthritis. Flexion Therapeutics Inc.
Ref 550497National Cancer Institute Drug Dictionary (drug id 747694).
Ref 550518National Cancer Institute Drug Dictionary (drug id 766123).
Ref 551954Clinical pipeline report, company report or official report of Loxo Oncology.

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