tyrosine kinase 2 | Janus kinase (JakA) family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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tyrosine kinase 2

  Target has curated data in GtoImmuPdb

Target id: 2269

Nomenclature: tyrosine kinase 2

Abbreviated Name: Tyk2

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 - 1187 19p13.2 TYK2 tyrosine kinase 2
Mouse - 1207 9 A3 Tyk2 tyrosine kinase 2
Rat - 1186 8q13 Tyk2 tyrosine kinase 2
Previous and Unofficial Names
JTK1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Non-phosphorylated TYK2 kinase with CMP6.
PDB Id:  3NZ0
Ligand:  JAK inhibitor I
Resolution:  2.0Å
Species:  Human
References:  30
Image of receptor 3D structure from RCSB PDB
Description:  Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6.
PDB Id:  3LXP
Ligand:  tofacitinib
Resolution:  1.65Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Tyk2 with compound 23
PDB Id:  6DBM
Ligand:  PF-06700841
Resolution:  2.368Å
Species:  Human
References:  12
Enzyme Reaction
EC Number: 2.7.10.2

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
example 1 [WO2016191524A1] Hs Inhibition 9.0 – 10.0 pKi 16
pKi 9.0 – 10.0 (Ki 1x10-9 – 1x10-10 M) [16]
delgocitinib Hs Inhibition 7.8 pKi 28
pKi 7.8 (Ki 1.4x10-8 M) [28]
Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [33P]ATP.
cerdulatinib Hs Inhibition 9.3 pIC50 8
pIC50 9.3 (IC50 5x10-10 M) [8]
JAK inhibitor I Hs Inhibition 9.0 pIC50 11
pIC50 9.0 (IC50 1x10-9 M) [11]
SAR-20347 Hs Inhibition 7.9 – 9.2 pIC50 1
pIC50 9.2 (IC50 6x10-10 M)
Description: In a 33P-ATP assay.
pIC50 7.9 (IC50 1.3x10-8 M) [1]
Description: In a TR-FRET assay.
compound 29 [Moslin et al., 2017] Hs Inhibition 8.4 pIC50 22
pIC50 8.4 (IC50 4x10-9 M) [22]
Description: Measuring binding to the JH2 pseudokinase domain of human TYK2.
ruxolitinib Hs Inhibition 7.5 – 9.3 pIC50 7,14
pIC50 9.3 (IC50 5.5x10-10 M) [14]
pIC50 7.5 (IC50 3x10-8 M) [7]
peficitinib Hs Inhibition 8.3 pIC50 18
pIC50 8.3 (IC50 5x10-9 M) [18]
TG02 Hs Inhibition 7.8 pIC50 13
pIC50 7.8 (IC50 1.4x10-8 M) [13]
ilginatinib Hs Inhibition 7.7 pIC50 24
pIC50 7.7 (IC50 2.2x10-8 M) [24]
PF-06700841 Hs Inhibition 7.6 pIC50 12
pIC50 7.6 (IC50 2.3x10-8 M) [12]
PF-06263276 Hs Inhibition 7.5 pIC50 19
pIC50 7.5 (IC50 2.97x10-8 M) [19]
JAK inhibitor 17b Hs Inhibition 7.4 pIC50 10
pIC50 7.4 (IC50 3.94x10-8 M) [10]
baricitinib Hs Inhibition 7.2 pIC50 7
pIC50 7.2 (IC50 6.1x10-8 M) [7]
BMS-911543 Hs Inhibition 7.2 pIC50 26
pIC50 7.2 (IC50 6.6x10-8 M) [26]
JAK inhibitor 20a Hs Inhibition 7.1 pIC50 10
pIC50 7.1 (IC50 7.37x10-8 M) [10]
oclacitinib Hs Inhibition 7.1 pIC50 3
pIC50 7.1 (IC50 7.51x10-8 M) [3]
fedratinib Hs Inhibition 6.8 pIC50 21
pIC50 6.8 (IC50 1.5x10-7 M) [21]
solcitinib Hs Inhibition 6.7 pIC50 4
pIC50 6.7 (IC50 2.19x10-7 M) [4]
tofacitinib Hs Inhibition 6.3 pIC50 7
pIC50 6.3 (IC50 4.89x10-7 M) [7]
Description: In a biochemical enzyme assay.
filgotinib Hs Inhibition 5.6 – 6.9 pIC50 7,31
pIC50 6.9 (IC50 1.16x10-7 M) [31]
pIC50 5.6 (IC50 2.6x10-6 M) [7]
upadacitinib Hs Inhibition 5.3 pIC50 32
pIC50 5.3 (IC50 4.7x10-6 M) [32]
JAK3 inhibitor 32 Hs Inhibition <5.0 pIC50 5
pIC50 <5.0 (IC50 >1x10-5 M) [5]
JAK3 inhibitor 34 Hs Inhibition <5.0 pIC50 5
pIC50 <5.0 (IC50 >1x10-5 M) [5]
Inhibitor Comments
The IC50 for decernotinib vs. TYK2 is >10 μM [7].
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 10.7 pKi 34
pKi 10.7 (Ki 2x10-11 M) [34]
Description: Determined in a Morrison titration by varying the concentration of the fluorescent probe in the TYK2 JH2 assay.
BMS-986165 Hs Inhibition 9.7 pIC50 34
pIC50 9.7 (IC50 2x10-10 M) [34]
Description: Binding to TYK2's JH2 pseudokinase domain in a biochemical binding assay.
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 9,33

Key to terms and symbols Click column headers to sort
Target used in screen: TYK2(JH1domain-catalytic)
Ligand Sp. Type Action Value Parameter
ruxolitinib Hs Inhibitor Inhibition 9.1 pKd
tofacitinib Hs Inhibitor Inhibition 8.3 pKd
JNJ-28312141 Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Hs Inhibitor Inhibition 7.8 pKd
fedratinib Hs Inhibitor Inhibition 7.7 pKd
staurosporine Hs Inhibitor Inhibition 7.3 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.1 pKd
dovitinib Hs Inhibitor Inhibition 6.8 pKd
KW-2449 Hs Inhibitor Inhibition 6.8 pKd
alvocidib Hs Inhibitor Inhibition 6.7 pKd
Target used in screen: TYK2(JH2domain-pseudokinase)
Ligand Sp. Type Action Value Parameter
alvocidib Hs Inhibitor Inhibition 7.5 pKd
dasatinib Hs Inhibitor Inhibition 7.0 pKd
sunitinib Hs Inhibitor Inhibition 6.4 pKd
fedratinib Hs Inhibitor Inhibition 6.3 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.3 pKd
MLN-120B Hs Inhibitor Inhibition 6.3 pKd
KW-2449 Hs Inhibitor Inhibition 6.3 pKd
SU-14813 Hs Inhibitor Inhibition 6.1 pKd
TG-100-115 Hs Inhibitor Inhibition 6.1 pKd
lestaurtinib Hs Inhibitor Inhibition 6.0 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.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: ...2

Key to terms and symbols Click column headers to sort
Target used in screen: nd/TYK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JNJ-7706621 Hs Inhibitor Inhibition 0.9
K-252a Hs Inhibitor Inhibition 0.9
JAK inhibitor I Hs Inhibitor Inhibition 1.5
staurosporine Hs Inhibitor Inhibition 1.9
Gö 6976 Hs Inhibitor Inhibition 2.6
SB 218078 Hs Inhibitor Inhibition 4.3
Cdk2 inhibitor IV Hs Inhibitor Inhibition 5.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 5.1
IKK-2 inhibitor IV Hs Inhibitor Inhibition 6.3
midostaurin Hs Inhibitor Inhibition 8.3
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and type II cytokine receptors, where it phosphorylates receptor subunits and facilitates signalling downstream of the receptors for the p40-containing cytokines IL-12 and IL-23 via activation of STAT-dependent transcription factors. It also mediates Type I IFN-driven responses [27]. TYK2 activity mediates cytokine-driven immune and pro-inflammatory signalling pathways that are key components in the cycle of chronic inflammation that drives the pathophysiology of immune-mediated diseases including psoriasis [17] and arthritic psoriasis, systemic lupus erythematosus and inflammatory bowel diseases.

Small molecules that inhibit TYK2 are being actively developed as novel therapeutics for the above conditions [15,23]. TYK2 selectivity has been achieved by targeting the protein's pseudokinase (Jak homology 2 or JH2) domain [20,29], rather than the functional kinase (or JH1) domain which shares a high degree of homology across all members of the Janus kinase family and offers little selectivity. Identified molecules act as negative allosteric modulators (NAM) of TYK2 activity. One particular example of a clinical candidate TYK2 NAM is BMS-986165, which is an orally active compound that has progressed to Phase 3 clinical evaluation in patients with psoriasis [25]. Clinical trials are in earlier stages for a spectrum of chronic autoimmune diseases. Click here to link to ClinicalTrials.gov's full list of BMS-986165 studies. As of June 2019 the chemical structure of BMS-986165 has not been formally disclosed.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0060337 type I interferon signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
GO:0035722 interleukin-12-mediated signaling pathway TAS
GO:0038155 interleukin-23-mediated signaling pathway TAS
GO:0060337 type I interferon signaling pathway TAS
GO:0070106 interleukin-27-mediated signaling pathway TAS
Clinically-Relevant Mutations and Pathophysiology
Disease:  Immunodeficiency 35; IMD35
Synonyms: Autosomal recessive hyper-IgE syndrome due to TYK2 deficiency [Orphanet: ORPHA331226]
Tyrosine kinase 2 deficiency
OMIM: 611521
Orphanet: ORPHA331226
Disease:  Juvenile rheumatoid factor-negative polyarthritis
Orphanet: ORPHA85408
Disease:  Oligoarticular juvenile arthritis
Orphanet: ORPHA85410

References

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1. A-González N, Castrillo A. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim. Biophys. Acta, 1812 (8): 982-94. [PMID:21193033]

2. 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]

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. 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]

6. Chrencik JE, Patny A, Leung IK, Korniski B, Emmons TL, Hall T, Weinberg RA, Gormley JA, Williams JM, Day JE et al.. (2010) Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6. J. Mol. Biol., 400 (3): 413-33. [PMID:20478313]

7. 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]

8. 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]

9. 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]

10. 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]

11. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20523-8. [PMID:18077363]

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. 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]

14. 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]

15. He X, Chen X, Zhang H, Xie T, Ye XY. (2019) Selective Tyk2 inhibitors as potential therapeutic agents: a patent review (2015-2018). Expert Opin Ther Pat, 29 (2): 137-149. [PMID:30621465]

16. 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.

17. Ishizaki M, Muromoto R, Akimoto T, Sekine Y, Kon S, Diwan M, Maeda H, Togi S, Shimoda K, Oritani K et al.. (2014) Tyk2 is a therapeutic target for psoriasis-like skin inflammation. Int. Immunol., 26 (5): 257-67. [PMID:24345760]

18. 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]

19. 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]

20. Liu C, Lin J, Moslin R, Tokarski JS, Muckelbauer J, Chang C, Tredup J, Xie D, Park H, Li P et al.. (2019) Identification of Imidazo[1,2-b]pyridazine Derivatives as Potent, Selective, and Orally Active Tyk2 JH2 Inhibitors. ACS Med Chem Lett, 10 (3): 383-388. [PMID:30891145]

21. 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]

22. Moslin R, Gardner D, Santella J, Zhang Y, Duncia JV, Liu C, Lin J, Tokarski JS, Strnad J, Pedicord D et al.. (2017) Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling. Medicinal Chemistry Communications, 8: 700-712. DOI: 10.1039/C6MD00560H

23. Moslin RM, Weinstein DS, Wrobleski ST, Tokarski JS, Kumar A. (2014) AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHα RESPONSES. Patent number: WO2014074661A1. Assignee: Bristol-Myers Squibb. Priority date: 08/11/2012. Publication date: 15/05/2014.

24. 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]

25. Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, Girgis IG, Kundu S, Banerjee S. (2018) Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N. Engl. J. Med., 379 (14): 1313-1321. [PMID:30205746]

26. 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]

27. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. (1998) How cells respond to interferons. Annu. Rev. Biochem., 67: 227-64. [PMID:9759489]

28. 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]

29. Tokarski JS, Zupa-Fernandez A, Tredup JA, Pike K, Chang C, Xie D, Cheng L, Pedicord D, Muckelbauer J, Johnson SR et al.. (2015) Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain. J. Biol. Chem., 290 (17): 11061-74. [PMID:25762719]

30. Tsui V, Gibbons P, Ultsch M, Mortara K, Chang C, Blair W, Pulk R, Stanley M, Starovasnik M, Williams D et al.. (2011) A new regulatory switch in a JAK protein kinase. Proteins, 79 (2): 393-401. [PMID:21117080]

31. 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]

32. 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.

33. 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]

34. 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., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.9b00444 [PMID:31318208]

How to cite this page

Janus kinase (JakA) family: tyrosine kinase 2. Last modified on 28/08/2019. Accessed on 17/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2269.