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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

Contents:

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 O60674 (Hs), Q62120 (Mm), Q62689 (Rn)
BRENDA 2.7.10.2
CATH/Gene3D 1.20.80.10, 3.30.505.10
ChEMBL Target CHEMBL2971 (Hs), CHEMBL1649049 (Mm), CHEMBL1075225 (Rn)
DrugBank Target O60674 (Hs)
Ensembl Gene ENSG00000096968 (Hs), ENSMUSG00000024789 (Mm), ENSRNOG00000059968 (Rn)
Entrez Gene 3717 (Hs), 16452 (Mm), 24514 (Rn)
Human Protein Atlas ENSG00000096968 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:3717 (Hs), mmu:16452 (Mm), rno:24514 (Rn)
OMIM 147796 (Hs)
Orphanet ORPHA122727 (Hs)
Pharos O60674 (Hs)
RefSeq Nucleotide NM_004972 (Hs), NM_001048177 (Mm), NM_031514 (Rn)
RefSeq Protein NP_004963 (Hs), NP_001041642 (Mm), NP_113702 (Rn)
SynPHARM 80886 (in complex with BMS-911543)
81944 (in complex with decernotinib)
85295 (in complex with decernotinib)
85292 (in complex with filgotinib)
80797 (in complex with filgotinib)
80436 (in complex with JAK inhibitor I)
85312 (in complex with JNJ-7706621)
85286 (in complex with PF-04965842)
85309 (in complex with PF-06263276)
85282 (in complex with tofacitinib)
UniProtKB O60674 (Hs), Q62120 (Mm), Q62689 (Rn)
Wikipedia JAK2 (Hs)
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:  66
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:  49
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:  72
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 70
⤷ pKd 7.5 (Kd 2.9x10-8 M) [70]
JNJ-7706621 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Binding 6.3 pKd 47,58
⤷ pKd 6.3 (Kd 4.56x10-7 M) [47]
Description: Affinity for JAK2 JH2 by competitive fluorescence polarization (FP) assay
pKd 6.3 (Kd 4.6x10-7 M) [58]
Description: Binding affinity for JAK2 JH2 pseudokinase domain
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 50
⤷ pKd 6.3 (Kd 4.6x10-7 M) [50]
compound 13 [PMID: 35653642] Small molecule or natural product Hs Binding 5.2 – 7.5 pKd 47
⤷ pKd 7.5 (Kd 3.34x10-8 M) [47]
Description: Binding affinity for JAK2 JH2 wild-type
pKd 5.2 (Kd 6.81x10-6 M) [47]
Description: Binding affinity for JAK2 JH1
compound 11 [PMID: 35653642] Small molecule or natural product Ligand has a PDB structure Hs Binding 5.5 – 7.1 pKd 47
⤷ pKd 7.1 (Kd 7.5x10-8 M) [47]
Description: Binding affinity for JAK2 JH2 wild-type
pKd 5.5 (Kd 3.36x10-6 M) [47]
Description: Binding affinity for JAK2 JH1 (active kinase domain)
nezulcitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 10.5 pKi 48
⤷ pKi 10.5 (Ki 3.1x10-11 M) [48]
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 36
⤷ pKi >10.0 (Ki <1x10-10 M) [36]
AZ960 Small molecule or natural product Primary target of this compound Hs Inhibition 9.4 pKi 30
⤷ pKi 9.4 (Ki 4.5x10-10 M) [30]
GDC-0214 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.2 pKi 20
⤷ pKi 9.2 (Ki 6.2x10-10 M) [20]
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 67
⤷ pKi 8.8 (Ki 1.7x10-9 M) [67]
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 15
⤷ pKi <5.5 (Ki >3.2x10-6 M) [15]
compound 18e [PMID: 31670517] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 86
⤷ pIC50 9.1 (IC50 7x10-10 M) [86]
ilginatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 54
⤷ pIC50 9.1 (IC50 7.2x10-10 M) [54]
tinengotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 83
⤷ pIC50 9.1 (IC50 7.5x10-10 M) [83]
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 69
⤷ pIC50 9.0 (IC50 1x10-9 M) [69]
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 59
⤷ pIC50 9.0 (IC50 1x10-9 M) [59]
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 77
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [77]
repotrectinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 21
⤷ pIC50 9.0 (IC50 1.04x10-9 M) [21]
AT-9283 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 34
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [34]
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 17,32,61
⤷ pIC50 8.6 – 9.6 (IC50 2.8x10-9 – 2.4x10-10 M) [32,61]
pIC50 8.1 (IC50 9x10-9 M) [17]
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 4
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [4]
CEP-33779 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 1.8x10-9 M) [22]
compound 25ap [PMID: 37796543] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 90
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [90]
XL019 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 25
⤷ pIC50 8.7 (IC50 2.2x10-9 M) [25]
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 56
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [56]
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 52,78
⤷ pIC50 8.5 (IC50 3x10-9 M) [52,78]
compound 19a [PMID: 24359159] Small molecule or natural product Click here for species-specific activity table Hs Inhibition >8.5 pIC50 66
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [66]
compound 13ac [PMID: 33256400] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 85
⤷ pIC50 8.5 (IC50 3x10-9 M) [85]
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 23
⤷ pIC50 8.4 (IC50 3.57x10-9 M) [23]
gandotinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 51
⤷ pIC50 8.4 (IC50 4x10-9 M) [51]
peficitinib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 37
⤷ pIC50 8.3 (IC50 5x10-9 M) [37]
ivarmacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 89
⤷ pIC50 8.3 (IC50 5x10-9 M) [89]
momelotinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 – 8.9 pIC50 3,57
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [3]
pIC50 7.7 (IC50 1.8x10-8 M) [57]
cerdulatinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 18
⤷ pIC50 8.2 (IC50 6x10-9 M) [18]
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 17,26
⤷ pIC50 8.2 (IC50 5.7x10-9 M) [26]
pIC50 8.1 (IC50 7x10-9 M) [17]
PF-956980 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 31
⤷ pIC50 8.1 (IC50 7.1x10-9 M) [31]
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 30
⤷ pIC50 8.1 (IC50 8x10-9 M) [30]
compound 30 [PMID: 37057760] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 60
⤷ pIC50 8.1 (IC50 8.36x10-9 M) [60]
lorpucitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 40
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [40]
Description: Determined in a biochemical high-throughput mass spectrometry (HTMS) assay.
compound 8l [PMID: 36053746] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 46
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [46]
oclacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.8 pIC50 7
⤷ pIC50 7.8 (IC50 1.75x10-8 M) [7]
rovadicitinib Small molecule or natural product Hs Inhibition >7.7 pIC50 44
⤷ pIC50 >7.7 (IC50 <2x10-8 M) [44]
Description: Binned value from patent; inhibition of WT hJAK2
pacritinib 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 7.6 pIC50 79
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [79]
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 39
⤷ pIC50 7.6 (IC50 2.31x10-8 M) [39]
JAK inhibitor 20a Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 23
⤷ pIC50 7.5 (IC50 2.96x10-8 M) [23]
WXFL10203614 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.0 – 8.0 pIC50 84
⤷ pIC50 7.0 – 8.0 (IC50 1x10-7 – 1x10-8 M) [84]
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 – 7.7 pIC50 29,80
⤷ pIC50 7.1 – 7.7 (IC50 7.3x10-8 – 1.9x10-8 M) [29,80]
CEE321 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 68
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [68]
RGB-286638 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 16
⤷ pIC50 7.3 (IC50 5x10-8 M) [16]
gusacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 73
⤷ pIC50 >7.3 (IC50 <5x10-8 M) [73]
solcitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 11
⤷ pIC50 7.2 (IC50 6.7x10-8 M) [11]
ropsacitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 28
⤷ pIC50 7.1 (IC50 7.4x10-8 M) [28]
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 17
⤷ pIC50 7.1 (IC50 7.7x10-8 M) [17]
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 24
⤷ pIC50 7.1 (IC50 7.7x10-8 M) [24]
itacitinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <7.0 pIC50 35
⤷ pIC50 <7.0 (IC50 >1x10-7 M) [35]
emzeltrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <7.0 pIC50 43
⤷ pIC50 <7.0 (IC50 >1x10-7 M) [43]
JNJ-7706621 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 58
⤷ pIC50 7.0 (IC50 1.06x10-7 M) [58]
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 74
⤷ pIC50 6.9 (IC50 1.2x10-7 M) [74]
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 17
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [17]
pIC50 6.2 (IC50 6.19x10-7 M) [17]
zemprocitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 76
⤷ pIC50 6.8 (IC50 1.413x10-7 M) [76]
TYK2 inhibitor 14l Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 88
⤷ pIC50 6.8 (IC50 1.57x10-7 M) [88]
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 17,71
⤷ pIC50 7.5 (IC50 2.8x10-8 M) [71]
pIC50 5.6 (IC50 2.4x10-6 M) [17]
girocitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 – 7.0 pIC50 45
⤷ pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [45]
safimaltib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 – 6.5 pIC50 42
⤷ pIC50 6.0 – 6.5 (IC50 1x10-6 – 3x10-7 M) [42]
abrocitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 72
⤷ pIC50 6.1 (IC50 8.03x10-7 M) [72]
SAR-20347 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 82
⤷ pIC50 6.1 (IC50 8.82x10-7 M) [82]
Description: In a TR-FRET assay.
itacnosertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.0 pIC50 53
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [53]
Description: Inhibitory activity against human JAK2 kinase, determined using a Z'-Lyte® biochemical assay.
londamocitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 55
⤷ pIC50 5.9 (IC50 1.22x10-6 M) [55]
JAK3 inhibitor 32 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 12
⤷ pIC50 5.5 (IC50 3.012x10-6 M) [12]
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 12
⤷ pIC50 <5.2 (IC50 >6.578x10-6 M) [12]
JAK3 inhibitor II Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.0 pIC50 14
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [14]
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 5
⤷ pIC50 5.0 (IC50 1x10-5 M) [5]
golidocitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.8 pIC50 65
⤷ pIC50 <4.8 (IC50 >1.5x10-5 M) [65]
Description: Inhbition of JAK2 enzymatic activity.
AC430 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition - - 33
⤷ [33]
deuruxolitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 75
⤷ [75]
Inhibitor Comments
Pacritinib inhibits JAK2V617F mutant with an IC50 of 19nM [79].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SJ988497 Small molecule or natural product Click here for species-specific activity table Hs Binding 9.5 pKd 13
⤷ pKd 9.5 (Kd 3.4x10-10 M) [13]
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: 19,81
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 Ligand has a PDB structure 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: 1,27
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 [8,10,63], as is IL-12/IL-23-driven Th1 and Th17 differentiation [8,63,87]. 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 [9]. 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 [64] and colitis-induced colorectal cancer [62].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Cellular signalling
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:  6,41
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:  6,38,41
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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