Jakinibs: A new class of kinase inhibitors in cancer and autoimmune disease

Current Opinion in Pharmacology

Volumn 12, Issue 4, 2012, Pages 464-470

  Kontzias, Apostolos ^a   Kotlyar, Alexander ^b   Laurence, Arian ^b   Changelian, Paul ^c   O'Shea, John J ^b  

^a Pediatric Rheumatology Branch   (United States)

^b NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES   (United States)

^c Infinity Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; AC 430; ADALIMUMAB; BARICITINIB; BMS 911543; CEP 33779; CYTOKINE RECEPTOR; CYTOKINE RECEPTOR 1; CYTOKINE RECEPTOR 2; DASATINIB; GLPG 0634; IMATINIB; JANUS KINASE; JANUS KINASE INHIBITOR; METHOTREXATE; MOMELOTINIB; N TERT BUTYL 3 [5 METHYL 2 [4 [2 (1 PYRROLIDINYL)ETHOXY]PHENYLAMINO] 4 PYRIMIDINYLAMINO]BENZENESULFONAMIDE; NILOTINIB; PACRITINIB; PLATELET DERIVED GROWTH FACTOR RECEPTOR; R 348; R 723; RUXOLITINIB; STEM CELL FACTOR RECEPTOR; SUNITINIB; TOFACITINIB; UNCLASSIFIED DRUG; VX 509;

ANEMIA; AUTOIMMUNE DISEASE; CANCER REGRESSION; CANCER RESISTANCE; CD8+ T LYMPHOCYTE; CHRONIC MYELOID LEUKEMIA; DRUG TARGETING; ENTERITIS; ENZYME INHIBITION; GASTROINTESTINAL STROMAL TUMOR; GLIOBLASTOMA; GRAFT REJECTION; GROWTH RETARDATION; HUMAN; HYPEREOSINOPHILIA; HYPERLIPIDEMIA; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; IMMUNOMODULATION; INFECTION; LYMPHOCYTOPENIA; LYMPHOMA; MALIGNANT NEOPLASTIC DISEASE; MYELOFIBROSIS; MYELOPROLIFERATIVE NEOPLASM; NEUTROPENIA; NONHUMAN; OPPORTUNISTIC INFECTION; POLYCYTHEMIA VERA; PRIORITY JOURNAL; PROTEIN BINDING; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; THROMBOTIC THROMBOCYTOPENIC PURPURA;

ANIMALS; ANTINEOPLASTIC AGENTS; AUTOIMMUNE DISEASES; GRAFT REJECTION; HUMANS; JANUS KINASES; MYELOPROLIFERATIVE DISORDERS; NEOPLASMS; PROTEIN KINASE INHIBITORS; RECEPTORS, CYTOKINE; SIGNAL TRANSDUCTION;

EID: 84864994569     PISSN: 14714892     EISSN: 14714973     Source Type: Journal    
DOI: 10.1016/j.coph.2012.06.008     Document Type: Review

References (65)

1. J.J. O'Shea, M. Gadina, and Y. Kanno Cytokine signaling: birth of a pathway J Immunol 187 2011 5475 5478
2. J.L. Boulay, J.J. O'Shea, and W.E. Paul Molecular phylogeny within type I cytokines and their cognate receptors Immunity 19 2003 159 163
3. W.J. Leonard, and J.J. O'Shea Jaks and STATs: biological implications Annu Rev Immunol 16 1998 293 322
4. J.E. Darnell Jr., I.M. Kerr, and G.R. Stark Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins Science 264 1994 1415 1421
5. D.E. Levy, and J.E. Darnell Jr. Stats: transcriptional control and biological impact Nat Rev Mol Cell Biol 3 2002 651 662
6. L. Velazquez, M. Fellous, G.R. Stark, and S. Pellegrini A protein tyrosine kinase in the interferon alpha/beta signaling pathway Cell 70 1992 313 322
7. W.J. Leonard, M. Noguchi, and S.M. Russell Sharing of a common gamma chain, gamma c, by the IL-2, IL-4, and IL-7 receptors: implications for X-linked severe combined immunodeficiency (XSCID) Adv Exp Med Biol 365 1994 225 232
8. S.M. Russell, N. Tayebi, H. Nakajima, M.C. Riedy, J.L. Roberts, M.J. Aman, T.S. Migone, M. Noguchi, M.L. Markert, and R.H. Buckley Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development Science 270 1995 797 800
9. P. Macchi, A. Villa, S. Giliani, M.G. Sacco, A. Frattini, F. Porta, A.G. Ugazio, J.A. Johnston, F. Candotti, and J.J. O'Shea Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID) Nature 377 1995 65 68
10. R.H. Buckley, R.I. Schiff, S.E. Schiff, M.L. Markert, L.W. Williams, T.O. Harville, J.L. Roberts, and J.M. Puck Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants J Pediatr 130 1997 378 387
11. K. Ghoreschi, A. Laurence, and J.J. O'Shea Janus kinases in immune cell signaling Immunol Rev 228 2009 273 287
12. B.J. Druker, and N.B. Lydon Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia J Clin Invest 105 2000 3 7
13. E. Buchdunger, C.L. Cioffi, N. Law, D. Stover, S. Ohno-Jones, B.J. Druker, and N.B. Lydon Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors J Pharmacol Exp Ther 295 2000 139 145
14. T. Schindler, W. Bornmann, P. Pellicena, W.T. Miller, B. Clarkson, and J. Kuriyan Structural mechanism for STI-571 inhibition of abelson tyrosine kinase Science 289 2000 1938 1942
15. B.J. Druker, F. Guilhot, S.G. O'Brien, I. Gathmann, H. Kantarjian, N. Gattermann, M.W. Deininger, R.T. Silver, J.M. Goldman, R.M. Stone, and F. Cervantes Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia N Engl J Med 355 2006 2408 2417
16. G.D. Demetri, M. von Mehren, C.D. Blanke, A.D. Van den Abbeele, B. Eisenberg, P.J. Roberts, M.C. Heinrich, D.A. Tuveson, S. Singer, M. Janicek, and J.A. Fletcher Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors N Engl J Med 347 2002 472 480
17. J. Cools, D.J. DeAngelo, J. Gotlib, E.H. Stover, R.D. Legare, J. Cortes, J. Kutok, J. Clark, I. Galinsky, J.D. Griffin, and N.C. Cross A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome N Engl J Med 348 2003 1201 1214
18. A. Hochhaus, H.M. Kantarjian, M. Baccarani, J.H. Lipton, J.F. Apperley, B.J. Druker, T. Facon, S.L. Goldberg, F. Cervantes, D. Niederwieser, and R.T. Silver Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy Blood 109 2007 2303 2309
19. G. Rosti, F. Castagnetti, G. Gugliotta, F. Palandri, G. Martinelli, and M. Baccarani Dasatinib and nilotinib in imatinib-resistant Philadelphia-positive chronic myelogenous leukemia: a 'head-to-head comparison' Leuk Lymphoma 51 2010 583 591
20. K. Ghoreschi, M.I. Jesson, X. Li, J.L. Lee, S. Ghosh, J.W. Alsup, J.D. Warner, M. Tanaka, S.M. Steward-Tharp, M. Gadina, and C.J. Thomas Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550) J Immunol 186 2011 4234 4243
21. M.W. Karaman, S. Herrgard, D.K. Treiber, P. Gallant, C.E. Atteridge, B.T. Campbell, K.W. Chan, P. Ciceri, M.I. Davis, P.T. Edeen, and R. Faraoni A quantitative analysis of kinase inhibitor selectivity Nat Biotechnol 26 2008 127 132
22. P.S. Changelian, M.E. Flanagan, D.J. Ball, C.R. Kent, K.S. Magnuson, W.H. Martin, B.J. Rizzuti, P.S. Sawyer, B.D. Perry, W.H. Brissette, and S.P. McCurdy Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor Science 302 2003 875 878
23. E. Kudlacz, B. Perry, P. Sawyer, M. Conklyn, S. McCurdy, W. Brissette, Flanagan, and P. Changelian The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models Am J Transplant 4 2004 51 57
24. A.J. Milici, E.M. Kudlacz, L. Audoly, S. Zwillich, and P. Changelian Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis Arthritis Res Ther 10 2008 R14
25. M.G. Boy, C. Wang, B.E. Wilkinson, V.F. Chow, A.T. Clucas, J.G. Krueger, A.S. Gaweco, S.H. Zwillich, P.S. Changelian, and G. Chan Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis J Invest Dermatol 129 2009 2299 2302
26. R. Fleischmann, M. Cutolo, M.C. Genovese, E.B. Lee, K.S. Kanik, S. Sadis, C.A. Connell, D. Gruben, S. Krishnaswami, G. Wallenstein, and B.E. Wilkinson Phase IIb dose-ranging study of the oral jak inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs Arthritis Rheum 64 2012 617 629
27. Y. Tanaka, M. Suzuki, H. Nakamura, S. Toyoizumi, and S.H. Zwillich Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate Arthritis Care Res 63 2011 1150 1158
28. D. Wojciechowski, and F. Vincenti Targeting JAK3 in kidney transplantation: current status and future options Curr Opin Organ Transplant 16 2011 614 619
29. J. Wollenhaupt, J.C. Silverfield, E.B. Lee, S. Wood, K. Soma, L. Wang, H. Nakamura, Y. Komuro, C.I. Nduaka, and D. Gruben Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, in the treatment of Rheumatoid arthritis: open label, long-term extension studies up to 36 months Arthritis Rheum 63 10 Suppl 2011 161 162
30. J. Kremer, Z-G. Li, S. Hall, R. Fleischmann, M. Genovese, E. Martin-Mola, J. Isaacs, D. Gruben, G. Wallenstein, and S. Krishnaswami Tofacitinib (CP-690,550), an oral Jak inhibitor, in combination with traditional DMARDs: Phase 3 study in patients with active rheumatoid arthritis with inadequate response to DMARDs Ann Rheum Dis 70 Suppl 3 2011 170
31. J.M. Kremer, S. Cohen, B.E. Wilkinson, C.A. Connell, J.L. French, J. Gomez-Reino, D. Gruben, K.S. Kanik, S. Krishnaswami, V. Pascual-Ramos, and G. Wallenstein A phase IIb dose-ranging study of the oral jak inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone Arthritis Rheum 64 2012 970 981
32. J.M. Kremer, B.J. Bloom, F.C. Breedveld, J.H. Coombs, M.P. Fletcher, D. Gruben, S. Krishnaswami, R. Burgos-Vargas, B. Wilkinson, C.A. Zerbini, and S.H. Zwillich The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo Arthritis Rheum 60 2009 1895 1905
33. D. van der Heijde, Y. Tanaka, R. Fleischmann, E.C. Keystone, J.M. Kremer, C.A.F. Zerbini, M. Cardiel, S.B. Cohen, P.T. Nash, and Y.W. Song Tofacitinib (CP-690,550), an oral janus kinase inhibitor, in combination with methotrexate reduced the progression of structural damage in patients with rheumatoid arthritis: a 24-month phase 3 study Arthritis Rheum 2011 2592
34. B.R. Burmester Gerd-Reudiger, C. Charles-Schoeman, J. Wollenhaupt, B. Zerbini, C.A.F. Benda, D. Gruben, G. Wallenstein, S. Krishnaswami, S.H. Zwillich, and T. Koncz Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, in combination with methotrexate, in patients with active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a 6-month phase 3 study Arthritis Rheum 63 10 Suppl 2011 288
35. E. Kudlacz, M. Conklyn, C. Andresen, C. Whitney-Pickett, and P. Changelian The JAK-3 inhibitor CP-690550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia Eur J Pharmacol 582 2008 154 161
36. S. Rosengren, M. Corr, G.S. Firestein, and D.L. Boyle The Jak inhibitor CP-690,550 (tofacitinib) inhibits tnf-induced chemokine expression in fibroblast-like synoviocytes: Autocrine role of type I interferon Ann Rheum Dis 71 2012 440 447
37. K. Maeshima, K. Yamaoka, S. Kubo, K. Nakano, S. Iwata, K. Saito, M. Ohishi, H. Miyahara, S. Tanaka, K. Ishii, and H. Yoshimatsu The jak inhibitor tofacitinib regulates synovitis through inhibition of interferon-gamma and interleukin-17 production by human CD4+ T cells Arthritis Rheum 64 2012 1790 1798
38. M. Conklyn, C. Andresen, P. Changelian, and E. Kudlacz The JAK3 inhibitor CP-690550 selectively reduces NK and CD8+ cell numbers in cynomolgus monkey blood following chronic oral dosing J Leukoc Biol 76 2004 1248 1255
39. R. Paniagua, M.S. Si, M.G. Flores, G. Rousvoal, S. Zhang, O. Aalami, A. Campbell, P.S. Changelian, B.A. Reitz, and D.C. Borie Effects of jak3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts Transplantation 80 2005 1283 1292
40. V.D. Sewgobind, M.E. Quaedackers, L.J. van der Laan, R. Kraaijeveld, S.S. Korevaar, G. Chan, W. Weimar, and C.C. Baan The Jak inhibitor CP-690,550 preserves the function of CD4CD25FoxP3 regulatory T cells and inhibits effector T cells Am J Transplant 10 2010 1785 1795
41. W. Williams, P. Scherle, J. Shi, R. Newton, E. McKeever, J. Fridman, T. Burn, K. Vaddi, R. Levy, and L. Moreland A randomized placebocontrolled study of INCB018424, a selective Janus kinase1& 2 (JAK1&2) inhibitor in rheumatoid arthritis Arthritis Rheum 58 2008 S431
42. R.A. Mesa Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis IDrugs 13 2010 394 403
43. M.W. Greenwald, R. Fidelus-Gort, R. Levy, J. Liang, K. Vaddi, W.V. William, and R. Newton A randomized dose-ranging, placebo-controlled study of INCB028050, a selective JAK1 and JAK2 inhibitor in subjects with active rheumatoid arthritis Arthritis Rheum 62 Suppl 10 2010 2172
44. G. Spencer-Green, F. Fan, B. Frankovic, X. Luo, T. Hoock, and N. Damjanov Dose ranging study of VX-509, an oral selective Jak3 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) Arthritis Rheum 63 Suppl 10 2011 L3
45. K.L. Stump, L.D. Lu, P. Dobrzanski, C. Serdikoff, D.E. Gingrich, B.J. Dugan, T.S. Angeles, M.S. Albom, M.A. Ator, B.D. Dorsey, and B.A. Ruggeri 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 2011 R68
46. L.D. Lu, K.L. Stump, N.H. Wallace, P. Dobrzanski, C. Serdikoff, D.E. Gingrich, B.J. Dugan, T.S. Angeles, M.S. Albom, J.L. Mason, and M.A. Ator Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2 J Immunol 187 2011 3840 3853
47. A. Tefferi, and A. Pardanani JAK inhibitors in myeloproliferative neoplasms: rationale, current data and perspective Blood Rev 25 2011 229 237
48. D. Ungureanu, J. Wu, T. Pekkala, Y. Niranjan, C. Young, O.N. Jensen, C.F. Xu, T.A. Neubert, R.C. Skoda, S.R. Hubbard, and O. Silvennoinen The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling Nat Struct Mol Biol 18 2011 971 976
49. S. Verstovsek, H. Kantarjian, R.A. Mesa, A.D. Pardanani, J. Cortes-Franco, D.A. Thomas, Z. Estrov, J.S. Fridman, E.C. Bradley, S. Erickson-Viitanen, and K. Vaddi Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis N Engl J Med 363 2010 1117 1127
50. C. Harrison, J.J. Kiladjian, H.K. Al-Ali, H. Gisslinger, R. Waltzman, V. Stalbovskaya, M. McQuitty, D.S. Hunter, R. Levy, L. Knoops, and F. Cervantes JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis N Engl J Med 366 2012 787 798
51. S. Verstovsek, R.A. Mesa, J. Gotlib, R.S. Levy, V. Gupta, J.F. DiPersio, J.V. Catalano, M. Deininger, C. Miller, R.T. Silver, and M. Talpaz A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis N Engl J Med 366 2012 799 807
52. A. Tefferi, M.R. Litzow, and A. Pardanani Long-term outcome of treatment with ruxolitinib in myelofibrosis N Engl J Med 365 2011 1455 1457
53. A. Quintas-Cardama, H. Kantarjian, J. Cortes, and S. Verstovsek Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond Nat Rev Drug Discov 10 2011 127 140
54. P.P. Zenatti, D. Ribeiro, W. Li, L. Zuurbier, M.C. Silva, M. Paganin, J. Tritapoe, J.A. Hixon, A.B. Silveira, B.A. Cardoso, and L.M. Sarmento Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia Nat Genet 43 2011 932 939
55. J. Zhang, L. Ding, L. Holmfeldt, G. Wu, S.L. Heatley, D. Payne-Turner, J. Easton, X. Chen, J. Wang, M. Rusch, and C. Lu The genetic basis of early T-cell precursor acute lymphoblastic leukaemia Nature 481 2012 157 163
56. M. Blink, T.D. Buitenkamp, M.M. van den Heuvel-Eibrink, A.A. Danen-van Oorschot, V. de Haas, D. Reinhardt, J.H. Klusmann, M. Zimmermann, M. Devidas, A.J. Carroll, and G. Basso Frequency and prognostic implications of JAK 1-3 aberrations in Down syndrome acute lymphoblastic and myeloid leukemia Leukemia 25 2011 1365 1368
57. H.L. Koskela, S. Eldfors, P. Ellonen, A.J. van Adrichem, H. Kuusanmaki, E.I. Andersson, S. Lagstrom, M.J. Clemente, T. Olson, S.E. Jalkanen, and M.M. Majumder Somatic STAT3 mutations in large granular lymphocytic leukemia N Engl J Med 366 2012 1905 1913
58. M. Hedvat, D. Huszar, A. Herrmann, J.M. Gozgit, A. Schroeder, A. Sheehy, R. Buettner, D. Proia, C.M. Kowolik, H. Xin, and B. Armstrong The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors Cancer Cell 16 2009 487 497
59. H. Xin, A. Herrmann, K. Reckamp, W. Zhang, S. Pal, M. Hedvat, C. Zhang, W. Liang, A. Scuto, S. Weng, and D. Morosini Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480 Cancer Res 71 2011 6601 6610
60. N. Stransky, A.M. Egloff, A.D. Tward, A.D. Kostic, K. Cibulskis, A. Sivachenko, G.V. Kryukov, M.S. Lawrence, C. Sougnez, A. McKenna, and E. Shefler The mutational landscape of head and neck squamous cell carcinoma Science 333 2011 1157 1160
61. T.S. Migone, J.X. Lin, A. Cereseto, J.C. Mulloy, J.J. O'Shea, G. Franchini, and W.J. Leonard Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I Science 269 1995 79 81
62. C.L. Yu, D.J. Meyer, G.S. Campbell, A.C. Larner, C. Carter-Su, J. Schwartz, and R. Jove Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein Science 269 1995 81 83
63. H. Yu, D. Pardoll, and R. Jove STATs in cancer inflammation and immunity: a leading role for STAT3 Nat Rev Cancer 9 2009 798 809
64. H. Lee, J. Deng, M. Kujawski, C. Yang, Y. Liu, A. Herrmann, M. Kortylewski, D. Horne, G. Somlo, S. Forman, and R. Jove STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors Nat Med 16 2010 1421 1428
65. F. Yang, C. Brown, R. Buettner, M. Hedvat, R. Starr, A. Scuto, A. Schroeder, M. Jensen, and R. Jove Sorafenib induces growth arrest and apoptosis of human glioblastoma cells through the dephosphorylation of signal transducers and activators of transcription 3 Mol Cancer Ther 9 2010 953 962