Janus kinase 2
Target id: 2048
Nomenclature: Janus kinase 2
Abbreviated Name: JAK2
Family: Janus kinase (JakA) family
Annotation status:
Annotated and awaiting review. Please contact us if you can help with reviewing.
» Email us
GtoImmuPdb view: OFF : Janus kinase 2 has curated GtoImmuPdb data
Contents:
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 |
| JTK10 |
| Database Links |
|
| BRENDA | 2.7.10.2 |
| CATH/Gene3D | 1.20.80.10, 3.30.505.10 |
| DrugBank Target | O60674 (Hs) |
| Ensembl Gene | ENSG00000096968 (Hs), ENSMUSG00000024789 (Mm), ENSRNOG00000015547 (Rn) |
| Entrez Gene | 3717 (Hs), 16452 (Mm), 24514 (Rn) |
| GenitoUrinary Development Molecular Anatomy Project | Jak2 (Mm) |
| 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) |
| 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) 80797 (in complex with filgotinib) 80436 (in complex with JAK inhibitor I) |
| UniProtKB | O60674 (Hs), Q62120 (Mm), Q62689 (Rn) |
| Wikipedia | JAK2 (Hs) |
| Selected 3D Structures |
|||||||||||||
|
|
||||||||||||
|
|
||||||||||||
|
|
||||||||||||
| Enzyme Reaction |
||||
|
||||
Download all structure-activity data for this target as a CSV file 
| Inhibitors | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inhibitor Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pacritinib inhibits JAK2V617F mutant with an IC50 of 19nM [40]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DiscoveRx KINOMEscan® screen |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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: 13,42 |
 
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Target used in screen: JAK2(JH1domain-catalytic) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: 1,17 |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Target used in screen: JAK2/JAK2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 [4,6,32], as is IL-12/IL-23-driven Th1 and Th17 differentiation [4,32,44]. 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 [5]. 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 [33] and colitis-induced colorectal cancer [31]. |
| Clinically-Relevant Mutations and Pathophysiology
|
||||||||||||||
|
||||||||||||||
|
||||||||||||||
|
||||||||||||||
|
||||||||||||||
|
||||||||||||||
|
||||||||||||||
References
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. 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.
4. 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]
5. 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., [Epub ahead of print]. [PMID:29382747]
6. 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]
7. 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.
8. 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]
9. 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]
10. 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]
11. 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]
12. 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]
13. 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]
14. 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]
15. 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]
16. 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]
17. 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]
18. 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]
19. 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]
20. 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]
21. 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.
22. 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]
23. 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.
24. 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]
25. 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]
26. 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]
27. 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]
28. 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]
29. 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]
30. 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]
31. 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]
32. 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]
33. 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]
34. Su Q, Ioannidis S, Chuaqui C, Almeida L, Alimzhanov M, Bebernitz G, Bell K, Block M, Howard T, Huang S et al.. (2013) Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors. J. Med. Chem., [Epub ahead of print]. [PMID:24359159]
35. 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]
36. 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]
37. 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]
38. 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]
39. 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]
40. 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[19.3.1.1(2,6).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]
41. 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[19.3.1.1(2,6).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]
42. 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]
43. 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]
44. 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]
How to cite this page
Janus kinase (JakA) family: Janus kinase 2. Last modified on 14/02/2018. Accessed on 26/04/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2048.
