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

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:  53
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:  38
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:  58
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 56
pKd 7.5 (Kd 2.9x10-8 M) [56]
BIIB068 Hs Inhibition 6.3 pKd 39
pKd 6.3 (Kd 4.6x10-7 M) [39]
izencitinib Hs Inhibition >10.0 pKi 32
pKi >10.0 (Ki <1x10-10 M) [32]
AZ960 Hs Inhibition 9.4 pKi 26
pKi 9.4 (Ki 4.5x10-10 M) [26]
delgocitinib Hs Inhibition 8.8 pKi 54
pKi 8.8 (Ki 1.7x10-9 M) [54]
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 13
pKi <5.5 (Ki >3.2x10-6 M) [13]
compound 18e [PMID: 31670517] Hs Inhibition 9.1 pIC50 67
pIC50 9.1 (IC50 7x10-10 M) [67]
ilginatinib Hs Inhibition 9.1 pIC50 43
pIC50 9.1 (IC50 7.2x10-10 M) [43]
JAK inhibitor I Hs Inhibition 9.0 pIC50 55
pIC50 9.0 (IC50 1x10-9 M) [55]
BMS-911543 Hs Inhibition 9.0 pIC50 47
pIC50 9.0 (IC50 1x10-9 M) [47]
compound 1d [PMID: 21493067] Hs Inhibition >9.0 pIC50 61
pIC50 >9.0 (IC50 <1x10-9 M) [61]
repotrectinib Hs Inhibition 9.0 pIC50 18
pIC50 9.0 (IC50 1.04x10-9 M) [18]
AT-9283 Hs Inhibition 8.9 pIC50 30
pIC50 8.9 (IC50 1.2x10-9 M) [30]
ruxolitinib Hs Inhibition 8.1 – 9.6 pIC50 15,28,48
pIC50 8.6 – 9.6 (IC50 2.8x10-9 – 2.4x10-10 M) [28,48]
pIC50 8.1 (IC50 9x10-9 M) [15]
LASW1393 Hs Inhibition 8.8 pIC50 3
pIC50 8.8 (IC50 1.5x10-9 M) [3]
CEP-33779 Hs Inhibition 8.7 pIC50 19
pIC50 8.7 (IC50 1.8x10-9 M) [19]
XL019 Hs Inhibition 8.7 pIC50 22
pIC50 8.7 (IC50 2.2x10-9 M) [22]
delgocitinib Hs Inhibition 8.6 pIC50 44
pIC50 8.6 (IC50 2.6x10-9 M) [44]
fedratinib Hs Inhibition 8.5 pIC50 41,62
pIC50 8.5 (IC50 3x10-9 M) [41,62]
compound 19a [PMID: 24359159] Hs Inhibition >8.5 pIC50 53
pIC50 >8.5 (IC50 <3x10-9 M) [53]
JAK inhibitor 17b Hs Inhibition 8.4 pIC50 20
pIC50 8.4 (IC50 3.57x10-9 M) [20]
gandotinib Hs Inhibition 8.4 pIC50 40
pIC50 8.4 (IC50 4x10-9 M) [40]
peficitinib Hs Inhibition 8.3 pIC50 33
pIC50 8.3 (IC50 5x10-9 M) [33]
cerdulatinib Hs Inhibition 8.2 pIC50 16
pIC50 8.2 (IC50 6x10-9 M) [16]
baricitinib 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 Hs Inhibition 8.1 pIC50 27
pIC50 8.1 (IC50 7.1x10-9 M) [27]
AZD1480 Hs Inhibition 8.1 pIC50 26
pIC50 8.1 (IC50 8x10-9 M) [26]
example 1 [WO2018112379A1] Hs Inhibition 8.1 pIC50 36
pIC50 8.1 (IC50 8.6x10-9 M) [36]
Description: Determined in a biochemical high-throughput mass spectrometry (HTMS) assay.
oclacitinib Hs Inhibition 7.8 pIC50 6
pIC50 7.8 (IC50 1.75x10-8 M) [6]
momelotinib Hs Inhibition 7.7 pIC50 45
pIC50 7.7 (IC50 1.8x10-8 M) [45]
pacritinib Hs Inhibition 7.6 pIC50 63
pIC50 7.6 (IC50 2.3x10-8 M) [63]
PF-06263276 Hs Inhibition 7.6 pIC50 35
pIC50 7.6 (IC50 2.31x10-8 M) [35]
JAK inhibitor 20a Hs Inhibition 7.5 pIC50 20
pIC50 7.5 (IC50 2.96x10-8 M) [20]
TG02 Hs Inhibition 7.1 – 7.7 pIC50 25,64
pIC50 7.1 – 7.7 (IC50 7.3x10-8 – 1.9x10-8 M) [25,64]
RGB-286638 Hs Inhibition 7.3 pIC50 14
pIC50 7.3 (IC50 5x10-8 M) [14]
gusacitinib Hs Inhibition >7.3 pIC50 59
pIC50 >7.3 (IC50 <5x10-8 M) [59]
solcitinib Hs Inhibition 7.2 pIC50 10
pIC50 7.2 (IC50 6.7x10-8 M) [10]
tofacitinib Hs Inhibition 7.1 pIC50 15
pIC50 7.1 (IC50 7.7x10-8 M) [15]
Description: In a biochemical enzyme assay.
brepocitinib Hs Inhibition 7.1 pIC50 21
pIC50 7.1 (IC50 7.7x10-8 M) [21]
itacitinib Hs Inhibition <7.0 pIC50 31
pIC50 <7.0 (IC50 >1x10-7 M) [31]
JNJ-7706621 Hs Binding 7.0 pIC50 46
pIC50 7.0 (IC50 1.06x10-7 M) [46]
Description: Binding to the JH2 pseudo kinase domain of JAK2 was determined using isothermal titration calorimetry (ITC).
upadacitinib Hs Inhibition 6.9 pIC50 60
pIC50 6.9 (IC50 1.2x10-7 M) [60]
decernotinib 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]
filgotinib Hs Inhibition 5.6 – 7.5 pIC50 15,57
pIC50 7.5 (IC50 2.8x10-8 M) [57]
pIC50 5.6 (IC50 2.4x10-6 M) [15]
abrocitinib Hs Inhibition 6.1 pIC50 58
pIC50 6.1 (IC50 8.03x10-7 M) [58]
SAR-20347 Hs Inhibition 6.1 pIC50 66
pIC50 6.1 (IC50 8.82x10-7 M) [66]
Description: In a TR-FRET assay.
example 11 [WO2014151871A9] Hs Inhibition <6.0 pIC50 42
pIC50 <6.0 (IC50 >1x10-6 M) [42]
Description: Inhibitory activity against human JAK2 kinase, determined using a Z'-Lyte® biochemical assay.
JAK3 inhibitor 32 Hs Inhibition 5.5 pIC50 11
pIC50 5.5 (IC50 3.012x10-6 M) [11]
JAK3 inhibitor 34 Hs Inhibition <5.2 pIC50 11
pIC50 <5.2 (IC50 >6.578x10-6 M) [11]
JAK3 inhibitor II Hs Inhibition <5.0 pIC50 12
pIC50 <5.0 (IC50 >1x10-5 M) [12]
GSK2646264 Hs Inhibition 5.0 pIC50 4
pIC50 5.0 (IC50 1x10-5 M) [4]
AZD4205 Hs Inhibition <4.8 pIC50 52
pIC50 <4.8 (IC50 >1.5x10-5 M) [52]
Description: Inhbition of JAK2 enzymatic activity.
AC430 Hs Inhibition - - 29
Inhibitor Comments
Pacritinib inhibits JAK2V617F mutant with an IC50 of 19nM [63].
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 17,65

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: 1,24

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 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 [7,9,50], as is IL-12/IL-23-driven Th1 and Th17 differentiation [7,50,68]. 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 [51] and colitis-induced colorectal cancer [49].
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 16 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:0042535 positive regulation of tumor necrosis factor biosynthetic process ISS
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:  5,37
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:  5,34,37
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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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. U.S.A., 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]

10. 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.

11. 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]

12. Changelian PS, Moshinsky D, Kuhn CF, Flanagan ME, Munchhof MJ, Harris TM, Whipple DA, Doty JL, Sun J, Kent CR et al.. (2008) The specificity of JAK3 kinase inhibitors. Blood, 111 (4): 2155-7. [PMID:18094329]

13. Chen H, Chan BK, Drummond J, Estrada AA, Gunzner-Toste J, Liu X, Liu Y, Moffat J, Shore D, Sweeney ZK et al.. (2012) Discovery of selective LRRK2 inhibitors guided by computational analysis and molecular modeling. J. Med. Chem., 55 (11): 5536-45. [PMID:22591441]

14. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

15. 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]

16. 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]

17. 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]

18. Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J et al.. (2018) Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov, 8 (10): 1227-1236. [PMID:30093503]

19. Dugan BJ, Gingrich DE, Mesaros EF, Milkiewicz KL, Curry MA, Zulli AL, Dobrzanski P, Serdikoff C, Jan M, Angeles TS et al.. (2012) A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779. J. Med. Chem., 55 (11): 5243-54. [PMID:22594690]

20. 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]

21. 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]

22. Forsyth T, Kearney PC, Kim BG, Johnson HW, Aay N, Arcalas A, Brown DS, Chan V, Chen J, Du H et al.. (2012) SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors. Bioorg. Med. Chem. Lett., 22 (24): 7653-8. [PMID:23127890]

23. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF et al.. (2010) Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J. Immunol., 184 (9): 5298-307. [PMID:20363976]

24. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

25. 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]

26. Gozgit JM, Bebernitz G, Patil P, Ye M, Parmentier J, Wu J, Su N, Wang T, Ioannidis S, Davies A et al.. (2008) Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2. J. Biol. Chem., 283 (47): 32334-43. [PMID:18775810]

27. Hanan EJ, Liang J, Wang X, Blake R, Blaquiere N, Staben ST. (2020) Monomeric targeted protein degraders. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c00093 [PMID:32352776]

28. 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]

29. Holladay MW, Setti E. (2014) Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof. Patent number: US8703943. Assignee: Ambit Biosciences Corporation. Priority date: 01/09/2010. Publication date: 22/04/2014.

30. Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL et al.. (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J. Med. Chem., 52 (2): 379-88. [PMID:19143567]

31. Huang T, Xue C-B, Wang A, Kong L, Ye HF, Yao W, Rodgers JD, Shepard S, Wang H, Shao L et al.. (2011) Piperidin-4-yl azetidine derivatives as jak1 inhibitors. Patent number: WO2011112662. Assignee: Incyte Corporation. Priority date: 10/03/2010. Publication date: 15/09/2011.

32. 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.

33. 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]

34. James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A et al.. (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature, 434 (7037): 1144-8. [PMID:15793561]

35. 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]

36. Koudriakova T, Kreutter K, Leonard K, Rizzolio M, Smith RC, Tichenor MS, Wang A. (2018) Small molecule inhibitors of the JAK family of kinases. Patent number: WO2018112379A1. Assignee: Janssen Pharmaceutica. Priority date: 16/12/2016. Publication date: 21/06/2018.

37. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC. (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med., 352 (17): 1779-90. [PMID:15858187]

38. Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE, Walter M, Burns CJ, Treutlein H, Wilks AF et al.. (2006) The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood, 107 (1): 176-83. [PMID:16174768]

39. Ma B, Bohnert T, Otipoby KL, Tien E, Arefayene M, Bai J, Bajrami B, Bame E, Chan TR, Humora M et al.. (2020) Discovery of BIIB068: A Selective, Potent, Reversible Bruton's Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c00702 [PMID:32696648]

40. Ma L, Clayton JR, Walgren RA, Zhao B, Evans RJ, Smith MC, Heinz-Taheny KM, Kreklau EL, Bloem L, Pitou C et al.. (2013) Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J, 3: e109. [PMID:23584399]

41. 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]

42. Mollard A, Warner SL, Flymm GA, Vankayalapati H, Bearss DJ. (2014) Jak2 and alk2 inhibitors and methods for their use. Patent number: WO2014151871A9. Assignee: Tolero Pharmaceuticals, Inc.. Priority date: 14/03/2013. Publication date: 31/12/2014.

43. 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]

44. Noji S, Hara Y, Miura T, Yamanaka H, Maeda K, Hori A, Yamamoto H, Obika S, Inoue M, Hase Y et al.. (2020) Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c00450 [PMID:32511913]

45. Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A. (2009) CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 23 (8): 1441-5. [PMID:19295546]

46. Puleo DE, Kucera K, Hammarén HM, Ungureanu D, Newton AS, Silvennoinen O, Jorgensen WL, Schlessinger J. (2017) Identification and Characterization of JAK2 Pseudokinase Domain Small Molecule Binders. ACS Med Chem Lett, 8 (6): 618-621. [PMID:28626521]

47. 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]

48. Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P et al.. (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood, 115 (15): 3109-17. [PMID:20130243]

49. Seavey MM, Lu LD, Stump KL, Wallace NH, Hockeimer W, O'Kane TM, Ruggeri BA, Dobrzanski P. (2012) Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer. Mol. Cancer Ther., 11 (4): 984-93. [PMID:22334590]

50. Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T, Verbeek M, Fischer J, Otten V, Schmickl M et al.. (2014) Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood, 123 (24): 3832-42. [PMID:24711661]

51. Stump KL, Lu LD, Dobrzanski P, Serdikoff C, Gingrich DE, Dugan BJ, Angeles TS, Albom MS, Ator MA, Dorsey BD et al.. (2011) A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis. Arthritis Res. Ther., 13 (2): R68. [PMID:21510883]

52. Su Q, Banks E, Bebernitz G, Bell K, Borenstein CF, Chen H, Chuaqui CE, Deng N, Ferguson AD, Kawatkar S et al.. (2020) Discovery of (2R)-N-[3-[2-[(3-Methoxy-1-methyl-pyrazol-4-yl)amino]pyrimidin-4-yl]-1H-indol-7-yl]-2-(4-methylpiperazin-1-yl)propenamide (AZD4205) as a Potent and Selective Janus Kinase 1 Inhibitor. J. Med. Chem., 63 (9): 4517-4527. [PMID:32297743]

53. Su Q, Ioannidis S, Chuaqui C, Almeida L, Alimzhanov M, Bebernitz G, Bell K, Block M, Howard T, Huang S et al.. (2014) Discovery of 1-methyl-1H-imidazole derivatives as potent Jak2 inhibitors. J. Med. Chem., 57 (1): 144-58. [PMID:24359159]

54. 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]

55. Thompson JE, Cubbon RM, Cummings RT, Wicker LS, Frankshun R, Cunningham BR, Cameron PM, Meinke PT, Liverton N, Weng Y et al.. (2002) Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg. Med. Chem. Lett., 12 (8): 1219-23. [PMID:11934592]

56. Tovar C, Higgins B, Deo D, Kolinsky K, Liu JJ, Heimbrook DC, Vassilev LT. (2010) Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle, 9 (16): 3364-75. [PMID:20814247]

57. 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]

58. Vazquez ML, Kaila N, Strohbach JW, Trzupek JD, Brown MF, Flanagan ME, Mitton-Fry MJ, Johnson TA, TenBrink RE, Arnold EP et al.. (2018) Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases. J. Med. Chem., 61 (3): 1130-1152. [PMID:29298069]

59. Venkatesan A, Smith RS, Hosahalli S, Potluri V, Panigrahi SK, Basetti V, Kuntu K. (2013) Pyrimido- pyridazinone compounds and use thereof. Patent number: WO2013028818A1. Assignee: Asana Biosciences LLC. Priority date: 23/08/2011. Publication date: 28/02/2013.

60. 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.

61. Wang T, Ioannidis S, Almeida L, Block MH, Davies AM, Lamb ML, Scott DA, Su M, Zhang HJ, Alimzhanov M et al.. (2011) In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg. Med. Chem. Lett., 21 (10): 2958-61. [PMID:21493067]

62. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J et al.. (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell, 13 (4): 311-20. [PMID:18394554]

63. William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET et al.. (2011) Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J. Med. Chem., 54 (13): 4638-58. [PMID:21604762]

64. William AD, Lee AC, Goh KC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Lee CP, Wang H, Williams M et al.. (2012) Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer. J. Med. Chem., 55 (1): 169-96. [PMID:22148278]

65. 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]

66. Works MG, Yin F, Yin CC, Yiu Y, Shew K, Tran TT, Dunlap N, Lam J, Mitchell T, Reader J et al.. (2014) Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J. Immunol., 193 (7): 3278-87. [PMID:25156366]

67. Yang T, Hu M, Qi W, Yang Z, Tang M, He J, Chen Y, Bai P, Yuan X, Zhang C et al.. (2019) Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms. J. Med. Chem., 62 (22): 10305-10320. [PMID:31670517]

68. Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu XZ. (2011) Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood, 118 (18): 5011-20. [PMID:21856864]

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Janus kinase (JakA) family: Janus kinase 2. Last modified on 12/08/2020. Accessed on 24/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2048.