tyrosine kinase 2 | Janus kinase (JakA) family | IUPHAR/BPS Guide to PHARMACOLOGY

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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
Database Links
ChEMBL 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:  Non-phosphorylated TYK2 kinase with CMP6.
PDB Id:  3NZ0
Ligand:  JAK inhibitor I
Resolution:  2.0Å
Species:  Human
References:  22
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.
Ligand:  tofacitinib
Resolution:  1.65Å
Species:  Human
References:  6
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
delgocitinib Hs Inhibition 7.8 pKi 21
pKi 7.8 (Ki 1.4x10-8 M) [21]
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 17
pIC50 8.4 (IC50 4x10-9 M) [17]
Description: Measuring binding to the JH2 pseudokinase domain of human TYK2.
ruxolitinib Hs Inhibition 7.5 – 9.3 pIC50 7,13
pIC50 9.3 (IC50 5.5x10-10 M) [13]
pIC50 7.5 (IC50 3x10-8 M) [7]
peficitinib Hs Inhibition 8.3 pIC50 14
pIC50 8.3 (IC50 5x10-9 M) [14]
TG02 Hs Inhibition 7.8 pIC50 12
pIC50 7.8 (IC50 1.4x10-8 M) [12]
ilginatinib Hs Inhibition 7.7 pIC50 18
pIC50 7.7 (IC50 2.2x10-8 M) [18]
PF-06263276 Hs Inhibition 7.5 pIC50 15
pIC50 7.5 (IC50 2.97x10-8 M) [15]
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 19
pIC50 7.2 (IC50 6.6x10-8 M) [19]
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 16
pIC50 6.8 (IC50 1.5x10-7 M) [16]
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 7,23
pIC50 6.9 (IC50 1.16x10-7 M) [23]
pIC50 5.6 (IC50 2.6x10-6 M) [7]
upadacitinib Hs Inhibition 5.3 pIC50 24
pIC50 5.3 (IC50 4.7x10-6 M) [24]
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].
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 9,25

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.


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 of cytokines including IL-6, IL-10 and IL-12 via the JAK-STAT pathway. It is also implicated in IFN-α signalling [20].
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


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How to cite this page

Janus kinase (JakA) family: tyrosine kinase 2. Last modified on 11/12/2018. Accessed on 15/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2269.