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 | |||||
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) | |||||
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 524232 | ClinicalTrials.gov (NCT01808157) A Study to Evaluate the Efficacy, Safety and Tolerability of CT327 in Atopic Dermatitis. U.S. National Institutes of Health. | ||||
Ref 524465 | ClinicalTrials.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 524734 | ClinicalTrials.gov (NCT02122913) Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Adult Solid Tumors. U.S. National Institutes of Health. | ||||
Ref 524973 | ClinicalTrials.gov (NCT02279433) A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b. U.S. National Institutes of Health. | ||||
Ref 532994 | ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol. 2014 Jul;12(7):429-39. | ||||
Ref 548789 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028850) | ||||
Ref 525414 | Topical 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 526991 | Bioorg 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 527569 | J 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 529647 | J 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). |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.