A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis

Arthritis Research and Therapy

Volumn 13, Issue 2, 2011, Pages

  Stump, Kristine L ^a   Lu, Lily D ^a   Dobrzanski, Pawel ^a   Serdikoff, Cynthia ^a   Gingrich, Diane E ^a   Dugan, Ben J ^a   Angeles, Thelma S ^a   Albom, Mark S ^a   Ator, Mark A ^a   Dorsey, Bruce D ^a   Ruggeri, Bruce A ^a   Seavey, Matthew M ^a  

^a CEPHALON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRHEUMATIC AGENT; AUTOANTIBODY; CEP 33779; COLLAGEN ANTIBODY; COLLAGEN TYPE 2; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 2; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; STAT3 PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; ENZYME INHIBITOR; PYRIDINE DERIVATIVE; TRIAZOLE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY BLOOD LEVEL; ARTICLE; BODY WEIGHT; ENZYME LINKED IMMUNOSORBENT ASSAY; EX VIVO STUDY; FEMALE; HELPER CELL; HISTOPATHOLOGY; MOUSE; NONHUMAN; OSTEOLYSIS; PANNUS; PAW EDEMA; PROTEIN PHOSPHORYLATION; RHEUMATOID ARTHRITIS; SCORING SYSTEM; SPLEEN; SYNOVIUM; ANIMAL; ARTHRITIS; DBA MOUSE; DISEASE MODEL; DRUG ANTAGONISM; IMMUNOLOGY; ORAL DRUG ADMINISTRATION; PATHOLOGY; WESTERN BLOTTING;

ADMINISTRATION, ORAL; ANIMALS; ANTI-INFLAMMATORY AGENTS; ARTHRITIS, EXPERIMENTAL; ARTHRITIS, RHEUMATOID; BLOTTING, WESTERN; DISEASE MODELS, ANIMAL; ENZYME INHIBITORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; JANUS KINASE 2; MICE; MICE, INBRED DBA; PYRIDINES; TRIAZOLES;

EID: 79954620949     PISSN: 14786354     EISSN: 14786362     Source Type: Journal    
DOI: 10.1186/ar3329     Document Type: Article

References (50)

1. Nathan C, Ding A. Nonresolving inflammation. Cell 2010, 140:871-882. 10.1016/j.cell.2010.02.029, 20303877.
2. Kundu JK, Surh YJ. Inflammation: gearing the journey to cancer. Mutat Res 2008, 659:15-30. 10.1016/j.mrrev.2008.03.002, 18485806.
3. Chan AC, Carter PJ. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 2010, 10:301-316. 10.1038/nri2761, 20414204.
4. Opar A. Kinase inhibitors attract attention as oral rheumatoid arthritis drugs. Nat Rev Drug Discov 2010, 9:257-258. 10.1038/nrd3155, 20357793.
5. Cohen S, Fleischmann R. Kinase inhibitors: a new approach to rheumatoid arthritis treatment. Curr Opin Rheumatol 2010, 22:330-335. 10.1097/BOR.0b013e3283378e6f, 20164774.
6. Bajpai M. Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases. IDrugs 2009, 12:174-185.
7. Bingham CO. Emerging therapeutics for rheumatoid arthritis. Bull NYU Hosp Jt Dis 2008, 66:210-215.
8. Oldfield V, Dhillon S, Plosker GL. Tocilizumab: a review of its use in the management of rheumatoid arthritis. Drugs 2009, 69:609-632. 10.2165/00003495-200969050-00007, 19368420.
9. Kerbleski JF, Gottlieb AB. Dermatological complications and safety of anti-TNF treatments. Gut 2009, 58:1033-1039. 10.1136/gut.2008.163683, 19592682.
10. Williams EL, Gadola S, Edwards CJ. Anti-TNF-induced lupus. Rheumatology (Oxford) 2009, 48:716-720.
11. Ramos-Casals M, Brito-Zeron P, Soto MJ, Cuadrado MJ, Khamashta MA. Autoimmune diseases induced by TNF-targeted therapies. Best Pract Res Clin Rheumatol 2008, 22:847-861. 10.1016/j.berh.2008.09.008, 19028367.
12. Walker JG, Smith MD. The Jak-STAT pathway in rheumatoid arthritis. J Rheumatol 2005, 32:1650-1653.
13. West K. CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders. Curr Opin Investig Drugs 2009, 10:491-504.
14. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis G, Newton RC, Metcalf B, Friedman SM, Vaddi K. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol 2010, 184:5298-5307. 10.4049/jimmunol.0902819, 20363976.
15. Uchiyama Y, Yorozu K, Hashizume M, Moriya Y, Mihara M. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorates joint swelling in established monkey collagen-induced arthritis. Biol Pharm Bull 2008, 31:1159-1163. 10.1248/bpb.31.1159, 18520048.
16. Curry MA, Dorsey BD, Dugan BJ, Gingrich DE, Mesaros EF, Mikiewicz KL. Preparation and Uses of 1,2,4-Triazolo [1,5a] Pyridine Derivatives (WO/2010/141796). 2010, Frazer, PA: Cephalon, Inc.
17. Hexner EO, Serdikoff C, Jan M, Swider CR, Robinson C, Yang S, Angeles T, Emerson SG, Carroll M, Ruggeri B, Dobrzanski P. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 2008, 111:5663-5671. 10.1182/blood-2007-04-083402, 2424161, 17984313.
18. Brand DD, Kang AH, Rosloniec EF. The mouse model of collagen-induced arthritis. Methods Mol Med 2004, 102:295-312.
19. Romano M, Faggioni R, Sironi M, Sacco S, Echtenacher B, Di Santo E, Salmona M, Ghezzi P. Carrageenan-induced acute inflammation in the mouse air pouch synovial model. Role of tumour necrosis factor. Mediators Inflamm 1997, 6:32-38. 10.1080/09629359791901, 2365839, 18472831.
20. Ellis L, Gilston V, Soo CC, Morris CJ, Kidd BL, Winyard PG. Activation of the transcription factor NF-κB in the rat air pouch model of inflammation. Ann Rheum Dis 2000, 59:303-307. 10.1136/ard.59.4.303, 1753107, 10733480.
21. Verdenius HH, Alma L. A quantitative study of decalcification methods in histology. J Clin Pathol 1958, 11:229-236. 10.1136/jcp.11.3.229, 479755, 13539226.
22. Eggert FM, Germain JP. Rapid demineralization in acidic buffers. Histochemistry 1979, 59:215-224. 10.1007/BF00495669, 107151.
23. Seavey MM, Maciag PC, Al-Rawi N, Sewell D, Paterson Y. An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2/neu+ breast tumors in a mouse model. J Immunol 2009, 182:5537-5546. 10.4049/jimmunol.0803742, 2850569, 19380802.
24. Vingsbo C, Larsson P, Andersson M, Holmdahl R. Association of pepsin with type II collagen (CII) breaks control of CII autoimmunity and triggers development of arthritis in rats. Scand J Immunol 1993, 37:337-342. 10.1111/j.1365-3083.1993.tb02562.x, 8441920.
25. Lu LD, Stump KL, Seavey MM. Novel method of monitoring trace cytokines and activated STAT molecules in the paws of arthritic mice using multiplex bead technology. BMC Immunol 2010, 11:55. 10.1186/1471-2172-11-55, 2992046, 21073728.
26. Fabian MA, Biggs WH, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA, Ciceri P, Edeen PT, Floyd M, Ford JM, Galvin M, Gerlach JL, Grotzfeld RM, Herrgard S, Insko DE, Insko MA, Lai AG, Lélias JM, Mehta SA, Milanov ZV, Velasco AM, Wodicka LM, Patel HK, Zarrinkar PP, Lockhart DJ. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 2005, 23:329-336. 10.1038/nbt1068, 15711537.
27. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008, 26:127-132. 10.1038/nbt1358, 18183025.
28. Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP, Jove R. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol 1998, 18:2545-2552. 110634, 9566874.
29. Lo HW, Hsu SC, Ali-Seyed M, Gunduz M, Xia W, Wei Y, Bartholomeusz G, Shih JY, Hung MC. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 2005, 7:575-589. 10.1016/j.ccr.2005.05.007, 15950906.
30. Kang I, Lee WW, Lee Y. Modulation of collagen-induced arthritis by IL-4 and dexamethasone: the synergistic effect of IL-4 and dexamethasone on the resolution of CIA. Immunopharmacology 2000, 49:317-324. 10.1016/S0162-3109(00)00248-4, 10996029.
31. Montesinos MC, Desai A, Cronstein BN. Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis. Arthritis Res Ther 2006, 8:R53. 10.1186/ar1914, 1526598, 16519795.
32. Douni E, Sfikakis PP, Haralambous S, Fernandes P, Kollias G. Attenuation of inflammatory polyarthritis in TNF transgenic mice by diacerein: comparative analysis with dexamethasone, methotrexate and anti-TNF protocols. Arthritis Res Ther 2004, 6:R65-R72. 10.1186/ar1028, 400419, 14979939.
33. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007, 7:429-442. 10.1038/nri2094, 17525752.
34. Cornelissen F, van Hamburg JP, Lubberts E. The IL-12/IL-23 axis and its role in Th17 cell development, pathology and plasticity in arthritis. Curr Opin Investig Drugs 2009, 10:452-462.
35. Singh R, Aggarwal A, Misra R. Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy. J Rheumatol 2007, 34:2285-2290.
36. Calero I, Nieto JA, Sanz I. B cell therapies for rheumatoid arthritis: beyond B cell depletion. Rheum Dis Clin North Am 2010, 36:325-343. 10.1016/j.rdc.2010.02.003, 20510237.
37. Alonzi T, Fattori E, Lazzaro D, Costa P, Probert L, Kollias G, De Benedetti F, Poli V, Ciliberto G. Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 1998, 187:461-468. 10.1084/jem.187.4.461, 2212160, 9463396.
38. Sasai M, Saeki Y, Ohshima S, Nishioka K, Mima T, Tanaka T, Katada Y, Yoshizaki K, Suemura M, Kishimoto T. Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice. Arthritis Rheum 1999, 42:1635-1643. 10.1002/1529-0131(199908)42:8<1635::AID-ANR11>3.0.CO;2-Q, 10446862.
39. Kagari T, Doi H, Shimozato T. The importance of IL-1β and TNF-α, and the noninvolvement of IL-6, in the development of monoclonal antibody-induced arthritis. J Immunol 2002, 169:1459-1466.
40. Fonseca JE, Santos MJ, Canhao H, Choy E. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 2009, 8:538-542. 10.1016/j.autrev.2009.01.012, 19189867.
41. O'Shea JJ, Park H, Pesu M, Borie D, Changelian P. New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway. Curr Opin Rheumatol 2005, 17:305-311. 10.1097/01.bor.0000160781.07174.db, 15838241.
42. O'Shea JJ, Murray PJ. Cytokine signaling modules in inflammatory responses. Immunity 2008, 28:477-487. 10.1016/j.immuni.2008.03.002, 2782488, 18400190.
43. Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T. Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK. Oncogene 1997, 14:2273-2282. 10.1038/sj.onc.1201071, 9178903.
44. Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y. Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity. J Biol Chem 1997, 272:14334-14340. 10.1074/jbc.272.22.14334, 9162069.
45. Sayeski PP, Ali MS, Safavi A, Lyles M, Kim SO, Frank SJ, Bernstein KE. A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn. J Biol Chem 1999, 274:33131-33142. 10.1074/jbc.274.46.33131, 10551884.
46. Fuhrer DK, Yang YC. Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11. Biochem Biophys Res Commun 1996, 224:289-296. 10.1006/bbrc.1996.1023, 8702385.
47. Ryu H, Lee JH, Kim KS, Jeong SM, Kim PH, Chung HT. Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin. J Immunol 2000, 165:2116-2123.
48. Haan S, Wuller S, Kaczor J, Rolvering C, Nocker T, Behrmann I, Haan C. SOCS-mediated downregulation of mutant Jak2 (V617F, T875N and K539L) counteracts cytokine-independent signaling. Oncogene 2009, 28:3069-3080. 10.1038/onc.2009.155, 19543316.
49. Ying M, Li D, Yang L, Wang M, Wang N, Chen Y, He M, Wang Y. Loss of SOCS3 expression is associated with an increased risk of recurrent disease in breast carcinoma. J Cancer Res Clin Oncol 2010, 136:1617-1626. 10.1007/s00432-010-0819-6, 20155426.
50. Isomaki P, Alanara T, Isohanni P, Lagerstedt A, Korpela M, Moilanen T, Visakorpi T, Silvennoinen O. The expression of SOCS is altered in rheumatoid arthritis. Rheumatology (Oxford) 2007, 46:1538-1546.