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

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Janus kinase 2

target has curated data in GtoImmuPdb

Target id: 2048

Nomenclature: Janus kinase 2

Abbreviated Name: JAK2

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 - 1132 9p24 JAK2 Janus kinase 2
Mouse - 1132 19 C1 Jak2 Janus kinase 2
Rat - 1132 1 q51-q53 Jak2 Janus kinase 2
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:  Structural basis of Jak2 inhibition by the type II inhibtor NVP-BBT594
Ligand:  NVP-BBT594
Resolution:  1.34Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors
PDB Id:  4C61
Ligand:  compound 19a [PMID: 24359159]
Resolution:  2.45Å
Species:  Human
References:  46
Image of receptor 3D structure from RCSB PDB
Description:  The structural basis of Janus Kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor (pyridone 6)
PDB Id:  2B7A
Ligand:  JAK inhibitor I
Resolution:  2.0Å
Species:  Human
References:  35
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of JAK2 in complex with compound 25
Ligand:  abrocitinib
Resolution:  1.8Å
Species:  Human
References:  51
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
RG-1530 Hs Inhibition 7.5 pKd 49
pKd 7.5 (Kd 2.9x10-8 M) [49]
example 1 [WO2016191524A1] Hs Inhibition >10.0 pKi 30
pKi >10.0 (Ki <1x10-10 M) [30]
AZ960 Hs Inhibition 9.4 pKi 25
pKi 9.4 (Ki 4.5x10-10 M) [25]
delgocitinib Hs Inhibition 8.8 pKi 47
pKi 8.8 (Ki 1.7x10-9 M) [47]
Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [33P]ATP.
HG-10-102-01 Hs Inhibition <5.5 pKi 12
pKi <5.5 (Ki >3.2x10-6 M) [12]
ilginatinib Hs Inhibition 9.1 pIC50 38
pIC50 9.1 (IC50 7.2x10-10 M) [38]
JAK inhibitor I Hs Inhibition 9.0 pIC50 48
pIC50 9.0 (IC50 1x10-9 M) [48]
BMS-911543 Hs Inhibition 9.0 pIC50 41
pIC50 9.0 (IC50 1x10-9 M) [41]
compound 1d [PMID: 21493067] Hs Inhibition >9.0 pIC50 54
pIC50 >9.0 (IC50 <1x10-9 M) [54]
TPX-0005 Hs Inhibition 9.0 pIC50 17
pIC50 9.0 (IC50 1.04x10-9 M) [17]
AT-9283 Hs Inhibition 8.9 pIC50 28
pIC50 8.9 (IC50 1.2x10-9 M) [28]
ruxolitinib Hs Inhibition 8.1 – 9.6 pIC50 14,26,42
pIC50 8.6 – 9.6 (IC50 2.8x10-9 – 2.4x10-10 M) [26,42]
pIC50 8.1 (IC50 9x10-9 M) [14]
CEP-33779 Hs Inhibition 8.7 pIC50 18
pIC50 8.7 (IC50 1.8x10-9 M) [18]
XL019 Hs Inhibition 8.7 pIC50 21
pIC50 8.7 (IC50 2.2x10-9 M) [21]
fedratinib Hs Inhibition 8.5 pIC50 37,55
pIC50 8.5 (IC50 3x10-9 M) [37,55]
compound 19a [PMID: 24359159] Hs Inhibition >8.5 pIC50 46
pIC50 >8.5 (IC50 <3x10-9 M) [46]
JAK inhibitor 17b Hs Inhibition 8.4 pIC50 19
pIC50 8.4 (IC50 3.57x10-9 M) [19]
gandotinib Hs Inhibition 8.4 pIC50 36
pIC50 8.4 (IC50 4x10-9 M) [36]
peficitinib Hs Inhibition 8.3 pIC50 31
pIC50 8.3 (IC50 5x10-9 M) [31]
cerdulatinib Hs Inhibition 8.2 pIC50 15
pIC50 8.2 (IC50 6x10-9 M) [15]
baricitinib Hs Inhibition 8.1 – 8.2 pIC50 14,22
pIC50 8.2 (IC50 5.7x10-9 M) [22]
pIC50 8.1 (IC50 7x10-9 M) [14]
AZD1480 Hs Inhibition 8.1 pIC50 25
pIC50 8.1 (IC50 8x10-9 M) [25]
oclacitinib Hs Inhibition 7.8 pIC50 5
pIC50 7.8 (IC50 1.75x10-8 M) [5]
momelotinib Hs Inhibition 7.7 pIC50 39
pIC50 7.7 (IC50 1.8x10-8 M) [39]
pacritinib Hs Inhibition 7.6 pIC50 56
pIC50 7.6 (IC50 2.3x10-8 M) [56]
PF-06263276 Hs Inhibition 7.6 pIC50 33
pIC50 7.6 (IC50 2.31x10-8 M) [33]
JAK inhibitor 20a Hs Inhibition 7.5 pIC50 19
pIC50 7.5 (IC50 2.96x10-8 M) [19]
TG02 Hs Inhibition 7.1 – 7.7 pIC50 24,57
pIC50 7.1 – 7.7 (IC50 7.3x10-8 – 1.9x10-8 M) [24,57]
RGB-286638 Hs Inhibition 7.3 pIC50 13
pIC50 7.3 (IC50 5x10-8 M) [13]
ASN002 Hs Inhibition >7.3 pIC50 52
pIC50 >7.3 (IC50 <5x10-8 M) [52]
solcitinib Hs Inhibition 7.2 pIC50 9
pIC50 7.2 (IC50 6.7x10-8 M) [9]
tofacitinib Hs Inhibition 7.1 pIC50 14
pIC50 7.1 (IC50 7.7x10-8 M) [14]
Description: In a biochemical enzyme assay.
PF-06700841 Hs Inhibition 7.1 pIC50 20
pIC50 7.1 (IC50 7.7x10-8 M) [20]
itacitinib Hs Inhibition <7.0 pIC50 29
pIC50 <7.0 (IC50 >1x10-7 M) [29]
JNJ-7706621 Hs Binding 7.0 pIC50 40
pIC50 7.0 (IC50 1.06x10-7 M) [40]
Description: Binding to the JH2 pseudo kinase domain of JAK2 was determined using isothermal titration calorimetry (ITC).
upadacitinib Hs Inhibition 6.9 pIC50 53
pIC50 6.9 (IC50 1.2x10-7 M) [53]
decernotinib Hs Inhibition 6.2 – 7.6 pIC50 14
pIC50 7.6 (IC50 2.4x10-8 M) [14]
pIC50 6.2 (IC50 6.19x10-7 M) [14]
filgotinib Hs Inhibition 5.6 – 7.5 pIC50 14,50
pIC50 7.5 (IC50 2.8x10-8 M) [50]
pIC50 5.6 (IC50 2.4x10-6 M) [14]
abrocitinib Hs Inhibition 6.1 pIC50 51
pIC50 6.1 (IC50 8.03x10-7 M) [51]
SAR-20347 Hs Inhibition 6.1 pIC50 59
pIC50 6.1 (IC50 8.82x10-7 M) [59]
Description: In a TR-FRET assay.
JAK3 inhibitor 32 Hs Inhibition 5.5 pIC50 10
pIC50 5.5 (IC50 3.012x10-6 M) [10]
JAK3 inhibitor 34 Hs Inhibition <5.2 pIC50 10
pIC50 <5.2 (IC50 >6.578x10-6 M) [10]
JAK3 inhibitor II Hs Inhibition <5.0 pIC50 11
pIC50 <5.0 (IC50 >1x10-5 M) [11]
GSK2646264 Hs Inhibition 5.0 pIC50 3
pIC50 5.0 (IC50 1x10-5 M) [3]
AC430 Hs Inhibition - - 27
Inhibitor Comments
Pacritinib inhibits JAK2V617F mutant with an IC50 of 19nM [56].
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 16,58

Key to terms and symbols Click column headers to sort
Target used in screen: JAK2(JH1domain-catalytic)
Ligand Sp. Type Action Value Parameter
ruxolitinib Hs Inhibitor Inhibition 10.4 pKd
tofacitinib Hs Inhibitor Inhibition 9.2 pKd
fedratinib Hs Inhibitor Inhibition 9.0 pKd
tamatinib Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Hs Inhibitor Inhibition 8.4 pKd
staurosporine Hs Inhibitor Inhibition 8.0 pKd
JNJ-28312141 Hs Inhibitor Inhibition 8.0 pKd
PP-242 Hs Inhibitor Inhibition 8.0 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.8 pKd
KW-2449 Hs Inhibitor Inhibition 7.1 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: 1,23

Key to terms and symbols Click column headers to sort
Target used in screen: JAK2/JAK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK inhibitor I Hs Inhibitor Inhibition 1.4 -1.0 1.0
staurosporine Hs Inhibitor Inhibition 1.9 0.0 -1.5
K-252a Hs Inhibitor Inhibition 3.0 2.0 -1.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 3.2 2.0 0.0
Cdk2 inhibitor IV Hs Inhibitor Inhibition 4.2 3.0 -1.0
tofacitinib Hs Inhibitor Inhibition 5.1
Gö 6976 Hs Inhibitor Inhibition 5.6 4.0 3.0
IKK-2 inhibitor IV Hs Inhibitor Inhibition 7.2 4.0 0.0
midostaurin Hs Inhibitor Inhibition 8.9 7.0 2.0
SB 218078 Hs Inhibitor Inhibition 14.2 86.0 82.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [6,8,44], as is IL-12/IL-23-driven Th1 and Th17 differentiation [6,44,60]. JAK2 is an alternative intervention point that can be manipulated to reduce pathogenic Th1/Th17 responses.

Genetic deletion or pharmacologic inhibition of JAK2 (using pacritinib) concomittantly enhances beneficial Th2 and Treg differentiation and efficiently impairs alloreactive Th1 responses, a combined effect that results in reduced GvHD lethality and extends the graft-versus-leukemia effect [7]. This beneficial effect is also observed in solid organ transplant models. The ffficacy of combining pacritinib with standard immune suppression (sirolimus/tacrolimus) after allogeneic hematopoietic cell transplantation is being evaluated in Phase 1/2 clinical trial NCT02891603.

CEP-33779, a selective JAK2 inhibitor has demonstrated efficacy in mouse models of rheumatoid arthritis [45] and colitis-induced colorectal cancer [43].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0050727 regulation of inflammatory response IDA
GO:0060333 interferon-gamma-mediated signaling pathway TAS
GO:0060334 regulation of interferon-gamma-mediated signaling pathway TAS
click arrow to show/hide IEA associations
GO:0050729 positive regulation of inflammatory response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0030218 erythrocyte differentiation ISS
GO:0050727 regulation of inflammatory response IDA
GO:0060334 regulation of interferon-gamma-mediated signaling pathway TAS
click arrow to show/hide IEA associations
GO:0050729 positive regulation of inflammatory response IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0030218 erythrocyte differentiation ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 13 GO processes
GO:0019221 cytokine-mediated signaling pathway IDA
GO:0032760 positive regulation of tumor necrosis factor production ISS
GO:0033209 tumor necrosis factor-mediated signaling pathway IDA
GO:0034612 response to tumor necrosis factor IDA
GO:0035722 interleukin-12-mediated signaling pathway IDA
GO:0038155 interleukin-23-mediated signaling pathway TAS
GO:0060333 interferon-gamma-mediated signaling pathway TAS
GO:0060334 regulation of interferon-gamma-mediated signaling pathway TAS
GO:0070102 interleukin-6-mediated signaling pathway TAS
GO:0070106 interleukin-27-mediated signaling pathway TAS
GO:0070671 response to interleukin-12 IDA
GO:0070757 interleukin-35-mediated signaling pathway TAS
click arrow to show/hide IEA associations
GO:0032731 positive regulation of interleukin-1 beta production IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
Immuno Disease Associations
Disease Name:  Myelofibrosis
Disease Synonyms:  no synonynms
Comment:  Somatic mutations in the JAK2 gene have been identified in many cases of myelofibrosis.
Disease X-refs:  Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824
References:  4,34
Disease Name:  Polycythemia vera
Disease Synonyms:  no synonynms
Comment:  Most cases of PV are associated with a somatic mutation in the JAK2 gene. The JAK2 V617F mutation causes constitutive tyrosine phosphorylation activity which promotes phenotypic changes consistent with PV pathology.
Disease X-refs:  Disease Ontology: DOID:8997
OMIM: 263300
Orphanet: ORPHA729
References:  4,32,34
Clinically-Relevant Mutations and Pathophysiology
Disease:  Acute myeloid leukemia
Synonyms: Acute myelogenous leukemia
Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
Disease:  Budd-Chiari syndrome
OMIM: 600880
Orphanet: ORPHA131
Disease:  Familial thrombocytosis
Description: A rare chronic myeloproliferative neoplasm (MPN) causing overproduction of platelets.
Synonyms: essential thrombocythaemia
hemorrhagic thrombocythemia
hereditary thrombocythemia
primary thrombocytosis
Disease Ontology: DOID:2224
Orphanet: ORPHA71493
Disease:  Myelofibrosis
Synonyms: Myelofibrosis with myeloid metaplasia [Orphanet: ORPHA824]
Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824
Disease:  Polycythemia vera
Disease Ontology: DOID:8997
OMIM: 263300
Orphanet: ORPHA729
Disease:  Thrombocythemia 3; THCYT3
Synonyms: Essential thrombocythemia [Orphanet: ORPHA3318]
Essential thrombocytosis [Orphanet: ORPHA3318]
OMIM: 614521
Orphanet: ORPHA3318


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Janus kinase (JakA) family: Janus kinase 2. Last modified on 28/08/2019. Accessed on 23/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2048.