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Janus kinase 2

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2048

Nomenclature: Janus kinase 2

Abbreviated Name: JAK2

Family: Janus kinase (JakA) family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1132 9p24.1 JAK2 Janus kinase 2
Mouse - 1129 19 23.73 cM Jak2 Janus kinase 2
Rat - 1132 1q52 Jak2 Janus kinase 2
Previous and Unofficial Names Click here for help
JTK10
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structural basis of Jak2 inhibition by the type II inhibtor NVP-BBT594
PDB Id:  3UGC
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:  55
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:  40
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of JAK2 in complex with compound 25
PDB Id:  6BBV
Ligand:  abrocitinib
Resolution:  1.8Å
Species:  Human
References:  60
Enzyme Reaction Click here for help
EC Number: 2.7.10.2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pKd 58
pKd 7.5 (Kd 2.9x10-8 M) [58]
BIIB068 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pKd 41
pKd 6.3 (Kd 4.6x10-7 M) [41]
nezulcitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 10.5 pKi 39
pKi 10.5 (Ki 3.1x10-11 M) [39]
izencitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >10.0 pKi 33
pKi >10.0 (Ki <1x10-10 M) [33]
AZ960 Small molecule or natural product Primary target of this compound Hs Inhibition 9.4 pKi 27
pKi 9.4 (Ki 4.5x10-10 M) [27]
delgocitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 pKi 56
pKi 8.8 (Ki 1.7x10-9 M) [56]
Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [33P]ATP.
HG-10-102-01 Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.5 pKi 13
pKi <5.5 (Ki >3.2x10-6 M) [13]
compound 18e [PMID: 31670517] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 71
pIC50 9.1 (IC50 7x10-10 M) [71]
ilginatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 45
pIC50 9.1 (IC50 7.2x10-10 M) [45]
JAK inhibitor I Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 57
pIC50 9.0 (IC50 1x10-9 M) [57]
BMS-911543 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 49
pIC50 9.0 (IC50 1x10-9 M) [49]
compound 1d [PMID: 21493067] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >9.0 pIC50 64
pIC50 >9.0 (IC50 <1x10-9 M) [64]
repotrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 18
pIC50 9.0 (IC50 1.04x10-9 M) [18]
AT-9283 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 31
pIC50 8.9 (IC50 1.2x10-9 M) [31]
ruxolitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 – 9.6 pIC50 15,29,50
pIC50 8.6 – 9.6 (IC50 2.8x10-9 – 2.4x10-10 M) [29,50]
pIC50 8.1 (IC50 9x10-9 M) [15]
LASW1393 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 3
pIC50 8.8 (IC50 1.5x10-9 M) [3]
CEP-33779 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 19
pIC50 8.7 (IC50 1.8x10-9 M) [19]
XL019 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 22
pIC50 8.7 (IC50 2.2x10-9 M) [22]
delgocitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 46
pIC50 8.6 (IC50 2.6x10-9 M) [46]
fedratinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 43,65
pIC50 8.5 (IC50 3x10-9 M) [43,65]
compound 19a [PMID: 24359159] Small molecule or natural product Click here for species-specific activity table Hs Inhibition >8.5 pIC50 55
pIC50 >8.5 (IC50 <3x10-9 M) [55]
compound 13ac [PMID: 33256400] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 70
pIC50 8.5 (IC50 3x10-9 M) [70]
Description: Inhibitory effect in a biochemical enzyme assay
JAK inhibitor 17b Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 20
pIC50 8.4 (IC50 3.57x10-9 M) [20]
gandotinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 42
pIC50 8.4 (IC50 4x10-9 M) [42]
peficitinib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 34
pIC50 8.3 (IC50 5x10-9 M) [34]
cerdulatinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 16
pIC50 8.2 (IC50 6x10-9 M) [16]
baricitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 – 8.2 pIC50 15,23
pIC50 8.2 (IC50 5.7x10-9 M) [23]
pIC50 8.1 (IC50 7x10-9 M) [15]
PF-956980 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 28
pIC50 8.1 (IC50 7.1x10-9 M) [28]
AZD1480 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 27
pIC50 8.1 (IC50 8x10-9 M) [27]
lorpucitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 37
pIC50 8.1 (IC50 8.6x10-9 M) [37]
Description: Determined in a biochemical high-throughput mass spectrometry (HTMS) assay.
oclacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.8 pIC50 6
pIC50 7.8 (IC50 1.75x10-8 M) [6]
momelotinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 47
pIC50 7.7 (IC50 1.8x10-8 M) [47]
pacritinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 66
pIC50 7.6 (IC50 2.3x10-8 M) [66]
PF-06263276 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 36
pIC50 7.6 (IC50 2.31x10-8 M) [36]
JAK inhibitor 20a Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 20
pIC50 7.5 (IC50 2.96x10-8 M) [20]
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 – 7.7 pIC50 26,67
pIC50 7.1 – 7.7 (IC50 7.3x10-8 – 1.9x10-8 M) [26,67]
RGB-286638 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 14
pIC50 7.3 (IC50 5x10-8 M) [14]
gusacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 61
pIC50 >7.3 (IC50 <5x10-8 M) [61]
solcitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 10
pIC50 7.2 (IC50 6.7x10-8 M) [10]
ropsacitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 25
pIC50 7.1 (IC50 7.4x10-8 M) [25]
tofacitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 15
pIC50 7.1 (IC50 7.7x10-8 M) [15]
Description: In a biochemical enzyme assay.
brepocitinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 21
pIC50 7.1 (IC50 7.7x10-8 M) [21]
itacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <7.0 pIC50 32
pIC50 <7.0 (IC50 >1x10-7 M) [32]
JNJ-7706621 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Binding 7.0 pIC50 48
pIC50 7.0 (IC50 1.06x10-7 M) [48]
Description: Binding to the JH2 pseudo kinase domain of JAK2 was determined using isothermal titration calorimetry (ITC).
upadacitinib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 62
pIC50 6.9 (IC50 1.2x10-7 M) [62]
decernotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.2 – 7.6 pIC50 15
pIC50 7.6 (IC50 2.4x10-8 M) [15]
pIC50 6.2 (IC50 6.19x10-7 M) [15]
TYK2 inhibitor 14l Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 73
pIC50 6.8 (IC50 1.57x10-7 M) [73]
filgotinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.6 – 7.5 pIC50 15,59
pIC50 7.5 (IC50 2.8x10-8 M) [59]
pIC50 5.6 (IC50 2.4x10-6 M) [15]
abrocitinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 60
pIC50 6.1 (IC50 8.03x10-7 M) [60]
SAR-20347 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 69
pIC50 6.1 (IC50 8.82x10-7 M) [69]
Description: In a TR-FRET assay.
itacnosertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.0 pIC50 44
pIC50 <6.0 (IC50 >1x10-6 M) [44]
Description: Inhibitory activity against human JAK2 kinase, determined using a Z'-Lyte® biochemical assay.
JAK3 inhibitor 32 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 11
pIC50 5.5 (IC50 3.012x10-6 M) [11]
JAK3 inhibitor 34 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <5.2 pIC50 11
pIC50 <5.2 (IC50 >6.578x10-6 M) [11]
JAK3 inhibitor II Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.0 pIC50 12
pIC50 <5.0 (IC50 >1x10-5 M) [12]
GSK2646264 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.0 pIC50 4
pIC50 5.0 (IC50 1x10-5 M) [4]
golidocitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.8 pIC50 54
pIC50 <4.8 (IC50 >1.5x10-5 M) [54]
Description: Inhbition of JAK2 enzymatic activity.
AC430 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition - - 30
[30]
deuruxolitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 63
[63]
Inhibitor Comments
Pacritinib inhibits JAK2V617F mutant with an IC50 of 19nM [66].
DiscoveRx KINOMEscan® screen Click here for help
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: 17,68

Key to terms and symbols Click column headers to sort
Target used in screen: JAK2(JH1domain-catalytic)
Ligand Sp. Type Action Value Parameter
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 10.4 pKd
tofacitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
KW-2449 Small molecule or natural product 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 Click here for help
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: 1,24

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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.4 -1.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.9 0.0 -1.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 3.0 2.0 -1.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.2 2.0 0.0
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.2 3.0 -1.0
tofacitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.1
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 4.0 3.0
IKK-2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 4.0 0.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 7.0 2.0
SB 218078 Small molecule or natural product 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 [7,9,52], as is IL-12/IL-23-driven Th1 and Th17 differentiation [7,52,72]. 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 [8]. 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 [53] and colitis-induced colorectal cancer [51].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 5 GO processes
GO:0001774 microglial cell activation ISS
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 3 GO processes
GO:0030099 myeloid cell differentiation IMP
GO:0030218 erythrocyte differentiation ISS
GO:0035166 post-embryonic hemopoiesis IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 15 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:0036016 cellular response to interleukin-3 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
GO:0097012 response to granulocyte macrophage colony-stimulating factor NAS
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 Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0001774 microglial cell activation ISS
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:  5,38
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:  5,35,38
Clinically-Relevant Mutations and Pathophysiology Click here for help
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

References

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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. Andraos R, Qian Z, Bonenfant D, Rubert J, Vangrevelinghe E, Scheufler C, Marque F, Régnier CH, De Pover A, Ryckelynck H et al.. (2012) Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent. Cancer Discov, 2 (6): 512-23. [PMID:22684457]

3. 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]

4. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al.. (2018) Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg Med Chem Lett, 28 (21): 3458-3462. [PMID:30249354]

5. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N et al.. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 365 (9464): 1054-61. [PMID:15781101]

6. 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.

7. Betts BC, Abdel-Wahab O, Curran SA, St Angelo ET, Koppikar P, Heller G, Levine RL, Young JW. (2011) Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen. Blood, 118 (19): 5330-9. [PMID:21917753]

8. Betts BC, Bastian D, Iamsawat S, Nguyen H, Heinrichs JL, Wu Y, Daenthanasanmak A, Veerapathran A, O'Mahony A, Walton K et al.. (2018) Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Proc Natl Acad Sci USA, 115 (7): 1582-1587. [PMID:29382747]

9. Betts BC, Sagatys EM, Veerapathran A, Lloyd MC, Beato F, Lawrence HR, Yue B, Kim J, Sebti SM, Anasetti C et al.. (2015) CD4+ T cell STAT3 phosphorylation precedes acute GVHD, and subsequent Th17 tissue invasion correlates with GVHD severity and therapeutic response. J Leukoc Biol, 97 (4): 807-19. [PMID:25663681]

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Janus kinase (JakA) family: Janus kinase 2. Last modified on 14/07/2021. Accessed on 20/09/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2048.