Target Information

Target General Infomation
Target ID
T62460
Former ID
TTDNS00611
Target Name
JAK1
Gene Name
JAK1
Synonyms
Janus kinase 1; Tyrosine-protein kinase JAK1; JAK1
Target Type
Clinical Trial
Disease Essential thrombocythemia [ICD9: 238.71, 289.9; ICD10: D47.3, D75.2, D75.8]
Malignancies [ICD9: 140-239; ICD10: C00-C96]
Psoriasis [ICD9: 696; ICD10: L40]
Polycythemia vera [ICD9: 238.4; ICD10: D45]
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Rheumatold arthritis; Psoriasis; Diabetic nephropathy [ICD9: 250, 250.4, 580-599, 696, 710-719, 714; ICD10: E08-E13, E10.2, E11.2, E13.2, L40, M00-M25, M05-M06, N00-N29]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Systemic lupus erythematosus [ICD9: 710; ICD10: M32]
Function
Tyrosine kinase of the non-receptor type, involved in theIFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
BioChemical Class
Kinase
UniProt ID
P23458
EC Number
EC 2.7.10.2
Sequence
MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRLGSGEYTAEEL
CIRAAQACRISPLCHNLFALYDENTKLWYAPNRTITVDDKMSLRLHYRMRFYFTNWHGTN
DNEQSVWRHSPKKQKNGYEKKKIPDATPLLDASSLEYLFAQGQYDLVKCLAPIRDPKTEQ
DGHDIENECLGMAVLAISHYAMMKKMQLPELPKDISYKRYIPETLNKSIRQRNLLTRMRI
NNVFKDFLKEFNNKTICDSSVSTHDLKVKYLATLETLTKHYGAEIFETSMLLISSENEMN
WFHSNDGGNVLYYEVMVTGNLGIQWRHKPNVVSVEKEKNKLKRKKLENKHKKDEEKNKIR
EEWNNFSYFPEITHIVIKESVVSINKQDNKKMELKLSSHEEALSFVSLVDGYFRLTADAH
HYLCTDVAPPLIVHNIQNGCHGPICTEYAINKLRQEGSEEGMYVLRWSCTDFDNILMTVT
CFEKSEQVQGAQKQFKNFQIEVQKGRYSLHGSDRSFPSLGDLMSHLKKQILRTDNISFML
KRCCQPKPREISNLLVATKKAQEWQPVYPMSQLSFDRILKKDLVQGEHLGRGTRTHIYSG
TLMDYKDDEGTSEEKKIKVILKVLDPSHRDISLAFFEAASMMRQVSHKHIVYLYGVCVRD
VENIMVEEFVEGGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNL
LLAREGIDSECGPFIKLSDPGIPITVLSRQECIERIPWIAPECVEDSKNLSVAADKWSFG
TTLWEICYNGEIPLKDKTLIEKERFYESRCRPVTPSCKELADLMTRCMNYDPNQRPFFRA
IMRDINKLEEQNPDIVSEKKPATEVDPTHFEKRFLKRIRDLGEGHFGKVELCRYDPEGDN
TGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGNGIKLIMEFLP
SGSLKEYLPKNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIG
DFGLTKAIETDKEYYTVKDDRDSPVFWYAPECLMQSKFYIASDVWSFGVTLHELLTYCDS
DSSPMALFLKMIGPTHGQMTVTRLVNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRT
SFQNLIEGFEALLK
Drugs and Mode of Action
Drug(s) Ruxolitinib Drug Info Phase 4 Essential thrombocythemia [523729], [541031]
ASP-015K Drug Info Phase 3 Psoriasis [525016], [543066]
Baricitinib Drug Info Phase 3 Rheumatold arthritis; Psoriasis; Diabetic nephropathy [524953], [542743]
Ruxolitinib Drug Info Phase 3 Pancreatic cancer [524723], [541031]
ABT-494 Drug Info Phase 2 Rheumatoid arthritis [525096]
GLPG-0634 Drug Info Phase 2 Rheumatoid arthritis [524620], [542835]
GSK2586184 Drug Info Phase 2 Systemic lupus erythematosus [524199]
INCB039110 Drug Info Phase 2 Malignancies [543090]
Ruxolitinib Drug Info Approved High-risk myelofibrosis [524601], [533122], [541031], [556264]
INCB47986 Drug Info Discontinued in Phase 2 Rheumatoid arthritis [549472]
Modulator ABT-494 Drug Info [532777]
Baricitinib Drug Info [532777]
GLPG-0634 Drug Info [532469], [532777]
GSK2586184 Drug Info [533157]
Ruxolitinib Drug Info [531783]
Inhibitor ASP-015K Drug Info [543544]
compound 19a Drug Info [532598]
INCB039110 Drug Info [543544]
INCB47986 Drug Info [532777]
WHI-P154 Drug Info [529228]
ZM-39923 Drug Info [525732]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway PI3K-Akt signaling pathway
Osteoclast differentiation
Signaling pathways regulating pluripotency of stem cells
Jak-STAT signaling pathway
Leishmaniasis
Toxoplasmosis
Tuberculosis
Hepatitis C
Hepatitis B
Measles
Influenza A
HTLV-I infection
Herpes simplex infection
Epstein-Barr virus infection
Pathways in cancer
Viral carcinogenesis
Pancreatic cancer
NetPath Pathway IL2 Signaling Pathway
PANTHER Pathway Angiogenesis
Interferon-gamma signaling pathway
JAK/STAT signaling pathway
PDGF signaling pathway
Pathway Interaction Database p73 transcription factor network
IL4-mediated signaling events
IL27-mediated signaling events
Signaling events mediated by TCPTP
SHP2 signaling
IL2-mediated signaling events
IL2 signaling events mediated by PI3K
IFN-gamma pathway
IL6-mediated signaling events
PDGFR-alpha signaling pathway
IL2 signaling events mediated by STAT5
Reactome Interleukin-6 signaling
MAPK3 (ERK1) activation
MAPK1 (ERK2) activation
GPVI-mediated activation cascade
ISG15 antiviral mechanism
Interleukin-7 signaling
gamma signalling through PI3Kgamma
Interleukin-2 signaling
RAF/MAP kinase cascade
Interferon gamma signaling
Regulation of IFNG signaling
Interferon alpha/beta signaling
Interleukin receptor SHC signaling
Regulation of IFNA signaling
WikiPathways Type II interferon signaling (IFNG)
Interferon type I signaling pathways
TGF Beta Signaling Pathway
IL-2 Signaling Pathway
IL-4 Signaling Pathway
IL-6 signaling pathway
TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
IL-3 Signaling Pathway
Interleukin-2 signaling
Interleukin-7 signaling
JAK/STAT
PDGF Pathway
Oncostatin M Signaling Pathway
Interleukin-11 Signaling Pathway
Prostate Cancer
TSLP Signaling Pathway
IL-9 Signaling Pathway
Type III interferon signaling
IL17 signaling pathway
IL-7 Signaling Pathway
Leptin signaling pathway
TSH signaling pathway
Integrated Breast Cancer Pathway
Integrated Cancer pathway
Interleukin-3, 5 and GM-CSF signaling
Interferon gamma signaling
Interferon alpha/beta signaling
IL-5 Signaling Pathway
References
Ref 523729ClinicalTrials.gov (NCT01493414) INC424 for Patients With Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis. U.S. National Institutes of Health.
Ref 524199ClinicalTrials.gov (NCT01777256) An Adaptive Phase II Study to Evaluate the Efficacy, Pharmacodynamics, Safety and Tolerability of GSK2586184. U.S. National Institutes of Health.
Ref 524601ClinicalTrials.gov (NCT02038036) Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.. U.S. National Institutes of Health.
Ref 524620ClinicalTrials.gov (NCT02048618) Efficacy and Safety of GLPG0634 in Subjects With Active Crohn's Disease. U.S. National Institutes of Health.
Ref 524723ClinicalTrials.gov (NCT02117479) Study of Ruxolitinib in Pancreatic Cancer Patients (Janus 1). U.S. National Institutes of Health.
Ref 524953ClinicalTrials.gov (NCT02265705) A Study of Baricitinib (LY3009104) in Participants With Rheumatoid Arthritis (RA). U.S. National Institutes of Health.
Ref 525016ClinicalTrials.gov (NCT02308163) A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs. U.S. National Institutes of Health.
Ref 525096ClinicalTrials.gov (NCT02365649) A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Anti-TNF Therapy (Celest Study). U.S. National Institutes of Health.
Ref 533122Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35.
Ref 541031(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: 5688).
Ref 542743(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: 7792).
Ref 542835(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: 7913).
Ref 543066(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: 8315).
Ref 543090(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: 8364).
Ref 549472Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038032)
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 525732Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett. 2000 Mar 20;10(6):575-9.
Ref 529228The specificity of JAK3 kinase inhibitors. Blood. 2008 Feb 15;111(4):2155-7. Epub 2007 Dec 19.
Ref 5317832011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
Ref 532469Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol. 2013 Oct 1;191(7):3568-77.
Ref 532598Discovery of 1-methyl-1H-imidazole derivatives as potent Jak2 inhibitors. J Med Chem. 2014 Jan 9;57(1):144-58.
Ref 532777Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
Ref 533157DRESS syndrome and reversible liver function abnormalities in patients with systemic lupus erythematosus treated with the highly selective JAK-1 inhibitor GSK2586184. Lupus. 2015 May;24(6):648-9.
Ref 543544(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: 2047).

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