Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6DM01)

• DTT Name: Janus kinase 1 (JAK-1)
• Synonyms: Tyrosine-protein kinase JAK1; JAK1B; JAK1A
• Gene Name: JAK1
• DTT Type: Successful target; [1]
• BioChemical Class: Kinase
• UniProt ID: JAK1_HUMAN
• TTD ID: T62460
• 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
• Function: Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor. Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway.
• KEGG Pathway:
  PI3K-Akt signaling pathway (hsa04151)
  Osteoclast differentiation (hsa04380)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Jak-STAT signaling pathway (hsa04630)
  Leishmaniasis (hsa05140)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  HTLV-I infection (hsa05166)
  Herpes simplex infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Pancreatic cancer (hsa05212)
• Reactome Pathway:
  MAPK3 (ERK1) activation (R-HSA-110056)
  MAPK1 (ERK2) activation (R-HSA-112411)
  GPVI-mediated activation cascade (R-HSA-114604)
  ISG15 antiviral mechanism (R-HSA-1169408)
  Interleukin-7 signaling (R-HSA-1266695)
  G beta (R-HSA-392451)
  Interleukin-2 signaling (R-HSA-451927)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interferon gamma signaling (R-HSA-877300)
  Regulation of IFNG signaling (R-HSA-877312)
  Interferon alpha/beta signaling (R-HSA-909733)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Regulation of IFNA signaling (R-HSA-912694)
  Interleukin-6 signaling (R-HSA-1059683)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Abrocitinib	DM8J29L	Atopic dermatitis	EA80	Approved	[2]
Baricitinib	DM4ONW5	Rheumatoid arthritis	FA20	Approved	[3]
Momelotinib	DMF98Q0	Myelofibrosis	2A20.2	Approved	[4]
Ruxolitinib	DM7Q98D	Essential thrombocythemia	3B63.1Z	Approved	[1]
Upadacitinib	DM32B5U	Rheumatoid arthritis	FA20	Approved	[5]

20 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP-015K	DMZ1UOI	Psoriasis vulgaris	EA90	Phase 3	[6]
SHR0302	DMUL8ZT	Ulcerative colitis	DD71	Phase 3	[7]
A223	DMHRS2O	Rheumatoid arthritis	FA20	Phase 2	[8]
ATI-501	DMTY6OF	Alopecia	ED70	Phase 2	[9]
ATI-502	DM8NODR	Alopecia	ED70	Phase 2	[10]
Cerdulatinib	DMSCR2H	B-cell lymphoma	2A86	Phase 2	[11]
CTP-543	DM3SYOK	Alopecia	ED70	Phase 2	[12]
EQ121	DMJN8UW	Rheumatoid arthritis	FA20	Phase 2	[13]
GLPG-0634	DMPHCDL	Crohn disease	DD70	Phase 2	[3]
GSK2586184	DMA2IXQ	Systemic lupus erythematosus	4A40.0	Phase 2	[14]
INCB039110	DMD9RV3	Malignant neoplasm	2A00-2F9Z	Phase 2	[6]
INCB54707	DMDK0HX	Hidradenitis suppurativa	ED92.0	Phase 2	[11]
PF-06700841	DMMGSFV	Asthma	CA23	Phase 2	[11]
TD-8236	DMTOMJN	Asthma	CA23	Phase 2	[15]
ALXN2075	DM1BSD8	Non-hodgkin lymphoma	2B33.5	Phase 1/2	[16]
AZD0449	DMGB1PL	Asthma	CA23	Phase 1	[17]
AZD4604	DMP3CSV	Asthma	CA23	Phase 1	[18]
GDC-0214	DMCNSII	Asthma	CA23	Phase 1	[19]
KN-002	DMK8FHB	Severe asthma	CA23	Phase 1	[20]
PF-07295324	DMBE63K	Atopic dermatitis	EA80	Phase 1	[21]

58 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminooxazole carboxamide derivative 1	DMDHGPN	N. A.	N. A.	Patented	[22]
Aminotriazolopyridine derivative 1	DMW2LZ0	N. A.	N. A.	Patented	[23]
Benzimidazole derivative 7	DMDK4RI	N. A.	N. A.	Patented	[23]
Bipyrazole derivative 1	DM6KGUB	N. A.	N. A.	Patented	[23]
Bis-aminopyrimidine derivative 1	DMQL34C	N. A.	N. A.	Patented	[23]
Bis-aminopyrimidine derivative 2	DMJXNO1	N. A.	N. A.	Patented	[23]
Bis-aminopyrimidine derivative 3	DMUNSYX	N. A.	N. A.	Patented	[23]
Bis-aminopyrimidine derivative 4	DMO1ZIG	N. A.	N. A.	Patented	[23]
Cyanomethyl pypazole carboxamide derivative 1	DMD198F	N. A.	N. A.	Patented	[22]
Cyclic cyanoethypypazole derivative 1	DM2BZI0	N. A.	N. A.	Patented	[22]
Cycloalkyl nitrile pyrazole carboxamide derivative 1	DM3RK0S	N. A.	N. A.	Patented	[22]
Cycloalkyl nitrile pyrazolo pyridone derivative 1	DMD3LK1	N. A.	N. A.	Patented	[22]
Cycloalkyl nitrile pyrazolo pyridone derivative 2	DMW4JB0	N. A.	N. A.	Patented	[22]
Cyclohexyl azetidine derivative 1	DMRBI5X	N. A.	N. A.	Patented	[23]
Five-and-six-membered heterocyclic compound 1	DM7SK5Q	N. A.	N. A.	Patented	[22]
Geminally-substituted cyanoethylpypazolo pyridone derivative 1	DMK6RFS	N. A.	N. A.	Patented	[22]
Geminally-substituted cyanoethylpypazolo pyridone derivative 2	DMB2INX	N. A.	N. A.	Patented	[22]
Imidazopyridazine derivative 1	DMEY6L8	N. A.	N. A.	Patented	[23]
Imidazopyridazine derivative 2	DMZORKY	N. A.	N. A.	Patented	[23]
Imidazo[4,5-c]pyridine derivative 1	DM4KBZQ	N. A.	N. A.	Patented	[23]
Imidazo[4,5-c]pyridine derivative 2	DMFDRJT	N. A.	N. A.	Patented	[23]
Isoxazole derivative 1	DMUMPZX	N. A.	N. A.	Patented	[22]
Isoxazole derivative 2	DMT842O	N. A.	N. A.	Patented	[22]
N-(cyanomethyl)-4-(2-(phenylamino)pyrimidin-4-yl)benzamide derivative 1	DM0OMAL	N. A.	N. A.	Patented	[23]
N-methylmethanesulfonamide derivative 1	DMIVK7D	N. A.	N. A.	Patented	[22]
PMID27774822-Compound-Figure11Example5	DMAHFXV	N. A.	N. A.	Patented	[22]
PMID27774822-Compound-Figure1Example20	DMCL19N	N. A.	N. A.	Patented	[22]
PMID27774822-Compound-Figure7Example63	DMF5IWB	N. A.	N. A.	Patented	[22]
PMID27774824-Compound-Figure11Example1up	DMH1W8F	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure2Example4	DMQHYMJ	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure3Example18	DMYZ6XQ	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure6Example12	DM1CM7S	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure6Example6	DMB18V5	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure7Example10	DMT85AH	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure9Example2down	DMXAV42	N. A.	N. A.	Patented	[23]
PMID27774824-Compound-Figure9Example2up	DME3TMS	N. A.	N. A.	Patented	[23]
Pyrazolopyridine derivative 3	DM2VQ4P	N. A.	N. A.	Patented	[22]
Pyrazolopyridine derivative 4	DMX7RWV	N. A.	N. A.	Patented	[22]
Pyrazolo[4,3-c]pyridine derivative 2	DMCDFLQ	N. A.	N. A.	Patented	[23]
Pyrimidopyridazinone derivative 2	DMD1RT0	N. A.	N. A.	Patented	[23]
Pyrrole derivative 7	DMZCERW	N. A.	N. A.	Patented	[22]
Pyrrole six-membered heteroaryl ring derivative 1	DM1A0VB	N. A.	N. A.	Patented	[22]
Pyrrolo-pyridine derivative 3	DMSNQEJ	N. A.	N. A.	Patented	[22]
Pyrrolo-pyridone derivative 1	DMR6QCE	N. A.	N. A.	Patented	[22]
Pyrrolo-pyridone derivative 2	DMCZ8UV	N. A.	N. A.	Patented	[22]
Pyrrolo-pyridone derivative 3	DMUIK3W	N. A.	N. A.	Patented	[22]
Pyrrolo[2,3-d]pyrimidine derivative 11	DM983CY	N. A.	N. A.	Patented	[23]
Pyrrolo[2,3-d]pyrimidine derivative 6	DM3D1L6	N. A.	N. A.	Patented	[22]
Pyrrolo[2,3-d]pyrimidine derivative 7	DM30Y8M	N. A.	N. A.	Patented	[22]
Pyrrolo[2,3-d]pyrimidine derivative 8	DMAW6KU	N. A.	N. A.	Patented	[22]
Ruxolitinib derivative 2	DMSJWZ3	N. A.	N. A.	Patented	[23]
Triazolo-pyridine derivative 1	DM0Q9VY	N. A.	N. A.	Patented	[22]
Tricyclic compound 1	DMLBR4F	N. A.	N. A.	Patented	[23]
Tricyclic compound 11	DMJAZ7D	N. A.	N. A.	Patented	[22]
Tricyclic compound 3	DM9K7P0	N. A.	N. A.	Patented	[23]
Tricyclic heterocycle derivative 1	DMXLJH4	N. A.	N. A.	Patented	[22]
Tricyclic heterocycle derivative 5	DMG1ESV	N. A.	N. A.	Patented	[22]
Tricyclic pyrrolopyridine compound 1	DMFIXW4	N. A.	N. A.	Patented	[22]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INCB47986	DMNRQA9	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[3]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID24359159C19a	DM26JYS	Discovery agent	N.A.	Investigative	[24]
WHI-P154	DMYHWS1	Diffuse large B-cell lymphoma	2A81	Investigative	[25]
ZM-39923	DMTMVYH	Discovery agent	N.A.	Investigative	[26]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Polycythemia vera	2C82	Whole blood	6.35E-07	-0.28	-1.07
Psoriasis	EA90	Skin	2.16E-02	-0.21	-0.36
Rheumatoid arthritis	FA20	Synovial tissue	5.55E-05	1.54	3.33

References

• [1] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [2] FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 213871.
• [3] Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.
• [4] FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216873
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [6] 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: 2047).
• [7] Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial. Am J Clin Dermatol. 2021 Nov;22(6):877-889.
• [8] Clinical pipeline report, company report or official report of Klus Pharma
• [9] Clinical pipeline report, company report or official report of Aclaris Therapeutics.
• [10] ClinicalTrials.gov (NCT03759340) ATI-502 Topical Solution for the Treatment of Alopecia Areata (AA), Alopecia Universalis (AU) and Alopecia Totalis (AT). U.S. National Institutes of Health.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] Clinical pipeline report, company report or official report of EQRx
• [14] DRESS 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.
• [15] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [16] The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2017 May 1;23(9):2313-2324.
• [17] Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma. Drug Des Devel Ther. 2022 Aug 31;16:2901-2917.
• [18] Clinical pipeline report, company report or official report of AstraZeneca
• [19] Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: A?randomized, controlled, proof-of-activity trial. J Allergy Clin Immunol. 2021 Sep;148(3):783-789.
• [20] Clinical pipeline report, company report or official report of Kinaset Therapeutics
• [21] Clinical pipeline report, company report or official report of Pfzer
• [22] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2.Expert Opin Ther Pat. 2017 Feb;27(2):145-161.
• [23] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [24] Discovery of 1-methyl-1H-imidazole derivatives as potent Jak2 inhibitors. J Med Chem. 2014 Jan 9;57(1):144-58.
• [25] The specificity of JAK3 kinase inhibitors. Blood. 2008 Feb 15;111(4):2155-7.
• [26] Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett. 2000 Mar 20;10(6):575-9.