Janus kinase 1 | Janus kinase (JakA) family | IUPHAR/BPS Guide to PHARMACOLOGY

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Janus kinase 1

target has curated data in GtoImmuPdb

Target id: 2047

Nomenclature: Janus kinase 1

Abbreviated Name: JAK1

Family: Janus kinase (JakA) family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1154 1p32.3-p31.3 JAK1 Janus kinase 1
Mouse - 1153 4 C6 Jak1 Janus kinase 1
Rat - 1153 5 q31.3-q35 Jak1 Janus kinase 1
Previous and Unofficial Names
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  JAK1 kinase (JH1 domain) in complex with compound 26
PDB Id:  4E5W
Resolution:  1.86Å
Species:  Human
References:  25
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of JAK1 in complex with compound 25
Ligand:  abrocitinib
Resolution:  2.08Å
Species:  Human
References:  37
Image of receptor 3D structure from RCSB PDB
Description:  Human JAK1 in complex with LASW1393
Ligand:  LASW1393
Resolution:  2.2Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Jak1 with compound 23
Ligand:  brepocitinib
Resolution:  2.48Å
Species:  Human
References:  12
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 5e [PMID: 28580438] Hs Inhibition 7.6 pKd 22
pKd 7.6 (Kd 2.8x10-8 M) [22]
Description: Measured using the JAK1 JH2 domain-pseudokinase.
izencitinib Hs Inhibition >10.0 pKi 19
pKi >10.0 (Ki <1x10-10 M) [19]
delgocitinib Hs Inhibition 8.7 pKi 34
pKi 8.7 (Ki 2.1x10-9 M) [34]
Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [33P]ATP.
example 1 [WO2018112379A1] Hs Inhibition 9.4 pIC50 24
pIC50 9.4 (IC50 4x10-10 M) [24]
Description: Determined in a biochemical high-throughput mass spectrometry (HTMS) assay.
ruxolitinib Hs Inhibition 8.2 – 10.1 pIC50 8,17,30
pIC50 8.5 – 10.1 (IC50 3.3x10-9 – 9x10-11 M) [17,30]
pIC50 8.2 (IC50 6x10-9 M) [8]
PF-06263276 Hs Inhibition 8.7 pIC50 23
pIC50 8.7 (IC50 2.2x10-9 M) [23]
AZD1480 Hs Inhibition >8.5 pIC50 20
pIC50 >8.5 (IC50 <3x10-9 M) [20]
compound 19a [PMID: 24359159] Hs Inhibition >8.5 pIC50 33
pIC50 >8.5 (IC50 <3x10-9 M) [33]
JAK inhibitor 20a Hs Inhibition 8.5 pIC50 11
pIC50 8.5 (IC50 3.37x10-9 M) [11]
peficitinib Hs Inhibition 8.4 pIC50 21
pIC50 8.4 (IC50 4x10-9 M) [21]
baricitinib Hs Inhibition 8.2 – 8.4 pIC50 8,14
pIC50 8.4 (IC50 4x10-9 M) [8]
pIC50 8.2 (IC50 5.9x10-9 M) [14]
itacitinib Hs Inhibition >8.3 pIC50 18
pIC50 >8.3 (IC50 <5x10-9 M) [18]
LASW1393 Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 5.5x10-9 M) [2]
solcitinib Hs Inhibition 8.2 pIC50 4
pIC50 8.2 (IC50 6.6x10-9 M) [4]
PF-956980 Hs Inhibition 8.1 pIC50 16
pIC50 8.1 (IC50 7.5x10-9 M) [16]
oclacitinib Hs Inhibition 8.0 pIC50 3
pIC50 8.0 (IC50 9.53x10-9 M) [3]
momelotinib Hs Inhibition 8.0 pIC50 28
pIC50 8.0 (IC50 1.1x10-8 M) [28]
upadacitinib Hs Inhibition 7.4 – 8.5 pIC50 38
pIC50 8.5 (IC50 3x10-9 M) [38]
Description: at 1uM ATP in a biochemical assay
pIC50 7.4 (IC50 4.3x10-8 M) [38]
cerdulatinib Hs Inhibition 7.9 pIC50 9
pIC50 7.9 (IC50 1.2x10-8 M) [9]
tofacitinib Hs Inhibition 7.8 pIC50 8
pIC50 7.8 (IC50 1.5x10-8 M) [8]
Description: In a biochemical enzyme assay.
brepocitinib Hs Inhibition 7.8 pIC50 12
pIC50 7.8 (IC50 1.7x10-8 M) [12]
compound 18e [PMID: 31670517] Hs Inhibition 7.6 pIC50 43
pIC50 7.6 (IC50 2.6x10-8 M) [43]
abrocitinib Hs Inhibition 7.5 pIC50 37
pIC50 7.5 (IC50 2.9x10-8 M) [37]
ilginatinib Hs Inhibition 7.5 pIC50 27
pIC50 7.5 (IC50 3.3x10-8 M) [27]
SAR-20347 Hs Inhibition 7.2 – 7.6 pIC50 41
pIC50 7.6 (IC50 2.3x10-8 M) [41]
Description: In a 33P-ATP assay.
pIC50 7.2 (IC50 5.9x10-8 M) [41]
Description: In a TR-FRET assay.
decernotinib Hs Inhibition 6.9 – 7.9 pIC50 8
pIC50 7.9 (IC50 1.32x10-8 M) [8]
pIC50 6.9 (IC50 1.12x10-7 M) [8]
TG02 Hs Inhibition 7.2 pIC50 15
pIC50 7.2 (IC50 5.9x10-8 M) [15]
filgotinib Hs Inhibition 6.4 – 8.0 pIC50 8,36
pIC50 8.0 (IC50 1x10-8 M) [36]
pIC50 6.4 (IC50 3.63x10-7 M) [8]
AZD4205 Hs Inhibition 7.2 pIC50 32
pIC50 7.2 (IC50 7x10-8 M) [32]
Description: Inhbition of JAK1 enzymatic activity.
fedratinib Hs Inhibition 7.0 pIC50 26
pIC50 7.0 (IC50 1x10-7 M) [26]
JAK inhibitor 17b Hs Inhibition 6.9 pIC50 11
pIC50 6.9 (IC50 1.25x10-7 M) [11]
XL019 Hs Inhibition 6.9 pIC50 13
pIC50 6.9 (IC50 1.343x10-7 M) [13]
NIK inhibitor 12f Hs Inhibition 6.7 pIC50 44
pIC50 6.7 (IC50 1.826x10-7 M) [44]
Description: Inhibitory concentration determined in a Reaction Biology kinase sreening assay.
BMS-911543 Hs Inhibition 6.4 pIC50 29
pIC50 6.4 (IC50 3.56x10-7 M) [29]
pacritinib Hs Inhibition 5.9 pIC50 39
pIC50 5.9 (IC50 1.28x10-6 M) [39]
ritlecitinib Hs Inhibition 5.8 pIC50 35
pIC50 5.8 (IC50 1.64x10-6 M) [35]
Description: At 1 mM ATP.
JAK3 inhibitor 32 Hs Inhibition 5.6 pIC50 6
pIC50 5.6 (IC50 2.703x10-6 M) [6]
JAK3 inhibitor 34 Hs Inhibition 5.5 pIC50 6
pIC50 5.5 (IC50 3.345x10-6 M) [6]
JAK3 inhibitor II Hs Inhibition <5.0 pIC50 7
pIC50 <5.0 (IC50 >1x10-5 M) [7]
JAK3 inhibitor IV Hs Inhibition 4.4 pIC50 5
pIC50 4.4 (IC50 3.981x10-5 M) [5]
Inhibitor Comments
Binding to JAK1 pseudokinase domain, although potent, produces low functional activity in a JAK1/JAK3 dependent IL-2 stimulated cellular assay [42].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BMS-986165 Hs Inhibition 9.0 pIC50 42
pIC50 9.0 (IC50 1x10-9 M) [42]
Description: Binding to JAK1 JH2 pseudokinase domain.
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 10,40

Key to terms and symbols Click column headers to sort
Target used in screen: JAK1(JH1domain-catalytic)
Ligand Sp. Type Action Value Parameter
tofacitinib Hs Inhibitor Inhibition 8.8 pKd
ruxolitinib Hs Inhibitor Inhibition 8.5 pKd
staurosporine Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Hs Inhibitor Inhibition 8.1 pKd
fedratinib Hs Inhibitor Inhibition 7.7 pKd
tamatinib Hs Inhibitor Inhibition 7.7 pKd
AST-487 Hs Inhibitor Inhibition 7.1 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.7 pKd
PP-242 Hs Inhibitor Inhibition 6.5 pKd
crizotinib Hs Inhibitor Inhibition 6.5 pKd
Target used in screen: JAK1(JH2domain-pseudokinase)
Ligand Sp. Type Action Value Parameter
sunitinib Hs Inhibitor Inhibition 7.3 pKd
SU-14813 Hs Inhibitor Inhibition 7.0 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.8 pKd
KW-2449 Hs Inhibitor Inhibition 6.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.5 pKd
dovitinib Hs Inhibitor Inhibition 6.4 pKd
pictilisib Hs Inhibitor Inhibition 6.4 pKd
TG-100-115 Hs Inhibitor Inhibition 6.2 pKd
fedratinib Hs Inhibitor Inhibition 5.7 pKd
PI-103 Hs Inhibitor Inhibition 5.7 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.


Reference: ...1

Key to terms and symbols Click column headers to sort
Target used in screen: nd/JAK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 1.8
staurosporine Hs Inhibitor Inhibition 2.1
tofacitinib Hs Inhibitor Inhibition 2.3
JAK inhibitor I Hs Inhibitor Inhibition 2.5
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 4.9
JNJ-7706621 Hs Inhibitor Inhibition 5.2
IKK-2 inhibitor IV Hs Inhibitor Inhibition 5.4
midostaurin Hs Inhibitor Inhibition 16.3
Gö 6976 Hs Inhibitor Inhibition 20.2
SB 218078 Hs Inhibitor Inhibition 22.2
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The JAK1 tyrosine kinase is crucial for signaling of certain type I and type II cytokines, via receptors belonging to the IL-2, IL-4 and IL-6 receptor families as well as neurotrophin-1 and leptin receptors (all type I cytokine receptors). JAK1 is also involved in signalling via type II IL-10 family receptors, and receptors for type I and type II interferons (IFN-α/β and IFN-γ respectively).
Immuno Process Associations
Immuno Process:  Inflammation
Comment:  JAK1 is crucial for mediating the intracellular signals for a range of type I and type II cytokines, and for type I and type II interferons (IFN-α/β and IFN-γ respectively) following ligand-receptor interaction.
GO Annotations:  Associated to 3 GO processes
GO:0060333 interferon-gamma-mediated signaling pathway TAS
GO:0060334 regulation of interferon-gamma-mediated signaling pathway TAS
GO:0060337 type I interferon signaling pathway TAS
Immuno Process:  Immune regulation
Comment:  JAK1 is crucial for mediating the intracellular signals for a range of type I and type II cytokines, and for type I and type II interferons (IFN-α/β and IFN-γ respectively) following ligand-receptor interaction.
GO Annotations:  Associated to 1 GO processes
GO:0060334 regulation of interferon-gamma-mediated signaling pathway TAS
Immuno Process:  Cytokine production & signalling
Comment:  JAK1 is crucial for mediating the intracellular signals for a range of type I and type II cytokines, and for type I and type II interferons (IFN-α/β and IFN-γ respectively) following ligand-receptor interaction.
GO Annotations:  Associated to 15 GO processes
GO:0019221 cytokine-mediated signaling pathway IBA
GO:0035722 interleukin-12-mediated signaling pathway TAS
GO:0035723 interleukin-15-mediated signaling pathway TAS
GO:0036016 cellular response to interleukin-3 IDA
GO:0038110 interleukin-2-mediated signaling pathway IDA
GO:0038111 interleukin-7-mediated signaling pathway TAS
GO:0038113 interleukin-9-mediated signaling pathway TAS
GO:0038114 interleukin-21-mediated signaling pathway TAS
GO:0060333 interferon-gamma-mediated signaling pathway TAS
GO:0060334 regulation of interferon-gamma-mediated signaling pathway TAS
GO:0060337 type I interferon signaling pathway TAS
GO:0070102 interleukin-6-mediated signaling pathway TAS
GO:0070106 interleukin-27-mediated signaling pathway TAS
GO:0070757 interleukin-35-mediated signaling pathway TAS
GO:0098761 cellular response to interleukin-7 IDA
Physiological Consequences of Altering Gene Expression
Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Jak1-/- cells fail to generate biologic responses to all class II cytokine receptors, cytokine receptors using the γc subunit or the IL6ST (gp130) subunits for signaling.
Species:  Mouse
Technique:  Gene knockout.
References:  31


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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Bach J, Eastwood P, González J, Gómez E, Alonso JA, Fonquerna S, Lozoya E, Orellana A, Maldonado M, Calaf E et al.. (2019) Identification of 2-Imidazopyridine and 2-Aminopyridone Purinones as Potent Pan-Janus Kinase (JAK) Inhibitors for the Inhaled Treatment of Respiratory Diseases. J. Med. Chem., 62 (20): 9045-9060. [PMID:31609613]

3. Berlinski PJ, Birchmeier MJ, Bowman JW, Gonzales AJ, Kamerling SG, Mann DW, Mitton-Fry MJ. (2010) Pyrrolo[2,3-d]pyrimidine compounds. Patent number: WO2010020905. Assignee: Pfizer Inc.. Priority date: 20/08/2008. Publication date: 25/02/2010.

4. Blanc J. (2010) Novel compound useful for the treatment of degenerative and inflammatory diseases. Patent number: WO2010149771. Assignee: Galapagos Nv, Menet, Christel Jeanne Marie. Priority date: 26/06/2009. Publication date: 29/12/2010.

5. Brown GR, Bamford AM, Bowyer J, James DS, Rankine N, Tang E, Torr V, Culbert EJ. (2000) Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg. Med. Chem. Lett., 10 (6): 575-9. [PMID:10741557]

6. Casimiro-Garcia A, Trujillo JI, Vajdos F, Juba B, Banker ME, Aulabaugh A, Balbo P, Bauman J, Chrencik J, Coe JW et al.. (2018) Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors. J. Med. Chem., 61 (23): 10665-10699. [PMID:30423248]

7. Changelian PS, Moshinsky D, Kuhn CF, Flanagan ME, Munchhof MJ, Harris TM, Whipple DA, Doty JL, Sun J, Kent CR et al.. (2008) The specificity of JAK3 kinase inhibitors. Blood, 111 (4): 2155-7. [PMID:18094329]

8. Clark JD, Flanagan ME, Telliez JB. (2014) Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J. Med. Chem., 57 (12): 5023-38. [PMID:24417533]

9. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, Hollenbach SJ, Pandey A, Sinha U. (2014) The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer. J. Pharmacol. Exp. Ther., 351 (3): 538-48. [PMID:25253883]

10. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

11. Elsayed MSA, Nielsen JJ, Park S, Park J, Liu Q, Kim CH, Pommier Y, Agama K, Low PS, Cushman M. (2018) Application of Sequential Palladium Catalysis for the Discovery of Janus Kinase Inhibitors in the Benzo[ c]pyrrolo[2,3- h][1,6]naphthyridin-5-one (BPN) Series. J. Med. Chem., 61 (23): 10440-10462. [PMID:30460842]

12. Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A et al.. (2018) Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J. Med. Chem., 61 (19): 8597-8612. [PMID:30113844]

13. Forsyth T, Kearney PC, Kim BG, Johnson HW, Aay N, Arcalas A, Brown DS, Chan V, Chen J, Du H et al.. (2012) SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors. Bioorg. Med. Chem. Lett., 22 (24): 7653-8. [PMID:23127890]

14. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF et al.. (2010) Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J. Immunol., 184 (9): 5298-307. [PMID:20363976]

15. Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD et al.. (2012) TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 26 (2): 236-43. [PMID:21860433]

16. Hanan EJ, Liang J, Wang X, Blake R, Blaquiere N, Staben ST. (2020) Monomeric targeted protein degraders. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c00093 [PMID:32352776]

17. Hanan EJ, van Abbema A, Barrett K, Blair WS, Blaney J, Chang C, Eigenbrot C, Flynn S, Gibbons P, Hurley CA et al.. (2012) Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors. J. Med. Chem., 55 (22): 10090-107. [PMID:23061660]

18. Huang T, Xue C-B, Wang A, Kong L, Ye HF, Yao W, Rodgers JD, Shepard S, Wang H, Shao L et al.. (2011) Piperidin-4-yl azetidine derivatives as jak1 inhibitors. Patent number: WO2011112662. Assignee: Incyte Corporation. Priority date: 10/03/2010. Publication date: 15/09/2011.

19. Hudson R, Kozak J, Fatheree PR, Podesto DD, Brandt GEL, Fleury M, Beausoleil A-M, Huang X, Thalladi VR. (2016) Naphthyridine compounds as jak kinase inhibitors. Patent number: WO2016191524A1. Assignee: Theravance Biopharma R&D. Priority date: 28/05/2015. Publication date: 01/12/2016.

20. Ioannidis S, Lamb ML, Wang T, Almeida L, Block MH, Davies AM, Peng B, Su M, Zhang HJ, Hoffmann E et al.. (2011) Discovery of 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the Jak/Stat pathway. J. Med. Chem., 54 (1): 262-76. [PMID:21138246]

21. Ito M, Yamazaki S, Yamagami K, Kuno M, Morita Y, Okuma K, Nakamura K, Chida N, Inami M, Inoue T et al.. (2017) A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model. J. Pharmacol. Sci., 133 (1): 25-33. [PMID:28117214]

22. Jarusiewicz JA, Jeon JY, Connelly MC, Chen Y, Yang L, Baker SD, Guy RK. (2017) Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia. ACS Omega, 2 (5): 1985-2009. [PMID:28580438]

23. Jones P, Storer RI, Sabnis YA, Wakenhut FM, Whitlock GA, England KS, Mukaiyama T, Dehnhardt CM, Coe JW, Kortum SW et al.. (2017) Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin. J. Med. Chem., 60 (2): 767-786. [PMID:27983835]

24. Koudriakova T, Kreutter K, Leonard K, Rizzolio M, Smith RC, Tichenor MS, Wang A. (2018) Small molecule inhibitors of the JAK family of kinases. Patent number: WO2018112379A1. Assignee: Janssen Pharmaceutica. Priority date: 16/12/2016. Publication date: 21/06/2018.

25. Kulagowski JJ, Blair W, Bull RJ, Chang C, Deshmukh G, Dyke HJ, Eigenbrot C, Ghilardi N, Gibbons P, Harrison TK et al.. (2012) Identification of imidazo-pyrrolopyridines as novel and potent JAK1 inhibitors. J. Med. Chem., 55 (12): 5901-21. [PMID:22591402]

26. Malerich JP, Lam JS, Hart B, Fine RM, Klebansky B, Tanga MJ, D'Andrea A. (2010) Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3. Bioorg. Med. Chem. Lett., 20 (24): 7454-7. [PMID:21106455]

27. Nakaya Y, Shide K, Niwa T, Homan J, Sugahara S, Horio T, Kuramoto K, Kotera T, Shibayama H, Hori K et al.. (2011) Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms. Blood Cancer J, 1 (7): e29. [PMID:22829185]

28. Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A. (2009) CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 23 (8): 1441-5. [PMID:19295546]

29. Purandare AV, McDevitt TM, Wan H, You D, Penhallow B, Han X, Vuppugalla R, Zhang Y, Ruepp SU, Trainor GL et al.. (2012) Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2. Leukemia., 26 (2): 280-8. [PMID:22015772]

30. Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P et al.. (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood, 115 (15): 3109-17. [PMID:20130243]

31. Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KC, Yin L, Pennica D et al.. (1998) Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell, 93 (3): 373-83. [PMID:9590172]

32. Su Q, Banks E, Bebernitz G, Bell K, Borenstein CF, Chen H, Chuaqui CE, Deng N, Ferguson AD, Kawatkar S et al.. (2020) Discovery of (2R)-N-[3-[2-[(3-Methoxy-1-methyl-pyrazol-4-yl)amino]pyrimidin-4-yl]-1H-indol-7-yl]-2-(4-methylpiperazin-1-yl)propenamide (AZD4205) as a Potent and Selective Janus Kinase 1 Inhibitor. J. Med. Chem., 63 (9): 4517-4527. [PMID:32297743]

33. Su Q, Ioannidis S, Chuaqui C, Almeida L, Alimzhanov M, Bebernitz G, Bell K, Block M, Howard T, Huang S et al.. (2014) Discovery of 1-methyl-1H-imidazole derivatives as potent Jak2 inhibitors. J. Med. Chem., 57 (1): 144-58. [PMID:24359159]

34. Tanimoto A, Ogawa Y, Oki C, Kimoto Y, Nozawa K, Amano W, Noji S, Shiozaki M, Matsuo A, Shinozaki Y et al.. (2015) Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. Inflamm. Res., 64 (1): 41-51. [PMID:25387665]

35. Thorarensen A, Dowty ME, Banker ME, Juba B, Jussif J, Lin T, Vincent F, Czerwinski RM, Casimiro-Garcia A, Unwalla R et al.. (2017) Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans. J. Med. Chem., 60 (5): 1971-1993. [PMID:28139931]

36. Van Rompaey L, Galien R, van der Aar EM, Clement-Lacroix P, Nelles L, Smets B, Lepescheux L, Christophe T, Conrath K, Vandeghinste N et al.. (2013) Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J. Immunol., 191 (7): 3568-77. [PMID:24006460]

37. Vazquez ML, Kaila N, Strohbach JW, Trzupek JD, Brown MF, Flanagan ME, Mitton-Fry MJ, Johnson TA, TenBrink RE, Arnold EP et al.. (2018) Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases. J. Med. Chem., 61 (3): 1130-1152. [PMID:29298069]

38. Voss JW, Camp HS, Padley RJ. (2015) Jak1 selective inhibitor and uses thereof. Patent number: WO2015061665. Assignee: Abbvie Inc.. Priority date: 24/10/2013. Publication date: 30/04/2015.

39. William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET et al.. (2011) Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J. Med. Chem., 54 (13): 4638-58. [PMID:21604762]

40. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

41. Works MG, Yin F, Yin CC, Yiu Y, Shew K, Tran TT, Dunlap N, Lam J, Mitchell T, Reader J et al.. (2014) Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J. Immunol., 193 (7): 3278-87. [PMID:25156366]

42. Wrobleski ST, Moslin R, Lin S, Zhang Y, Spergel S, Kempson J, Tokarski JS, Strnad J, Zupa-Fernandez A, Cheng L et al.. (2019) Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165. J. Med. Chem., 62 (20): 8973-8995. [PMID:31318208]

43. Yang T, Hu M, Qi W, Yang Z, Tang M, He J, Chen Y, Bai P, Yuan X, Zhang C et al.. (2019) Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms. J. Med. Chem., 62 (22): 10305-10320. [PMID:31670517]

44. Zhu Y, Ma Y, Zu W, Song J, Wang H, Zhong Y, Li H, Zhang Y, Gao Q, Kong B et al.. (2020) Identification of N-phenyl-7H-pyrrolo[2,3-d] pyrimidin-4-amine Derivatives as Novel, Potent, and Selective NF-κB Inducing Kinase (NIK) Inhibitors for the Treatment of Psoriasis. J. Med. Chem., [Epub ahead of print]. [PMID:32479083]

How to cite this page

Janus kinase (JakA) family: Janus kinase 1. Last modified on 16/06/2020. Accessed on 03/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2047.