Kinase inhibitors for the treatment of inflammatory and autoimmune disorders

Purinergic Signalling

Volumn 5, Issue 1, 2009, Pages 107-115

  Bhagwat, Shripad S ^a  

^a Ambit Biosciences   (United States)

Author keywords

Anti inflammatory agents; Autoimmunemodulators; IKK2 inhibitors; JAK3 inhibitors; Kinase inhibitors; Lck inhibitors; Syk inhibitors

Indexed keywords

EID: 60449117455     PISSN: 15739538     EISSN: 15739546     Source Type: Journal    
DOI: 10.1007/s11302-008-9117-z     Document Type: Review

References (58)

1. Goldstein DM, Gray NS, Zarrinkar PP (2008) High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov 7:391-397
2. Karaman MW, Herrgard S, Treiber DK et al (2008) A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 26:127-132
3. Bhagwat SS (2007) MAP kinase inhibitors in inflammation and autoimmune disorders. Ann Rep Med Chem 42:265-278
4. Strnad J, Burke JR (2007) IκB kinase inhibitors for treating autoimmune and inflammatory disorders: Potential and challenges. Trends Pharmacol Sci 28:142-148
5. Lavon I, Goldberg I, Amit S et al (2000) High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-κB activation. Nat Med 6:573-577
6. Burke JR, Pattoli MA, Gregor KR et al (2003) BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice. J Biol Chem 278:1450-1456
7. MacMaster JF, Dambach DM, Lee DB et al (2003) An inhibitor of IκB kinase, BMS-345541, blocks endothelial cell adhesion molecule expression and reduces the severity of dextran sulfate sodium-induced colitis in mice. Inflamm Res 52:508-511
8. Beaulieu F, Ouellet C, Ruediger EH et al (2007) Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors. Bioorg Med Chem Lett 17:1233-1237
9. Belema M, Bunker A, Nguyen VN et al (2007) Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2-e)pyrazines as IKK-β inhibitors. Bioorg Med Chem Lett 17:4284-4289
10. Bingham AH, Davenport RJ, Gowers L et al (2004) A novel series of potent and selective IKK2 inhibitors. Bioorg Med Chem Lett 14:409-412
11. Murata T, Shimada M, Sakakibara S et al (2004) Synthesis and structure-activity relationships of novel IKK-β inhibitors. Part 3: orally active anti-inflammatory agents. Bioorg Med Chem Lett 14:4019-4022
12. Murata T, Shimada M, Kadono H et al (2004) Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 2: improvement of in vitro activity. Bioorg Med Chem Lett 14:4013-4018
13. Murata T, Shimada M, Sakakibara S et al (2003) Discovery of novel and selective IKK-serine-threonine protein kinase inhibitors. Bioorg Med Chem Lett 13:913-916
14. Ziegelbauer K, Gantner F, Lukas NW et al (2005) A selective novel low-molecular-weight inhibitor of IκB kinase-β (IKK-β) prevents pulmonary inflammation and slows broad anti-inflammatory activity. Br J Pharmacol 145:178-192
15. Kishore N, Sommers C, Mathialagan S et al (2003) A selective IKK-2 inhibitor blocks NF-κB-dependent gene expression in interleukin-1b-stimulated synovial fibroblasts. J Biol Chem 278:32861-32871
16. Bonafoux D, Bonar S, Christine L et al (2005) Inhibition of IKK-2 by 2-[(aminocarbonyl)amino]-acetylenyl-3-thiophenecarboxamides. Bioorg Med Chem Lett 15:2870-2875
17. Podolin PL, Callahan JF, Bolognese BJ et al (2005) Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IκB kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluophenyl)-3-thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell proliferation. J Pharmacol Exp Ther 312:373-381
18. Baxter A, Brough S, Cooper A et al (2004) Hit-to-lead studies: The discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors. Bioorg Med Chem Lett 14:2817-2822
19. Waelchli R, Bollbuck B, Bruns C et al (2006) Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK. Bioorg Med Chem Lett 16:108-112
20. Bhagwat SS, Bennett BL, Satoh Y et al (2001) The small molecule IKK2 inhibitor SPC-839 is efficacious in an animal model of arthritis. A paper presented at ACR Annual Scientific Meeting, San Francisco
21. Frelin C, Imbert V, Greissinger E et al (2003) AS602868, a pharmacological inhibitor of IKK2, reveals the apoptotic potential of TNF-α in Jurkat leukemic cells. Oncogene 22:8187-8194
22. Castro AF, Dang LC, Soucy F et al (2003) Novel IKK inhibitors: β-carbolines. Bioorg Med Chem Lett 13:2419-2422
23. Wong BR, Grossbard EB, Payan DG, Masuda ES (2004) Targeting Syk as a treatment for allergic and autoimmune disorders. Expert Opin Investig Drugs 13:743-762
24. Lai JYQ, Cox PJ, Patel R et al (2003) Potent small molecule inhibitors of spleen tyrosine kinase (Syk). Bioorg Med Chem Lett 13:3111-3114
25. Cywin CL, Zhao B-P, McNeil DW et al (2003) Discovery and SAR of novel [1,6]naphthyridines as potent inhibitors of spleen tyrosine kinase (SYK). Bioorg Med Chem Lett 13:1415-1418
26. Yamamoto N, Takeshita K, Shichijo M et al (2003) The orally available spleen tyrosine kinase inhibitor 2-[7-(3,4-dimethoxyphenyl) -imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide dihydrochloride (BAY 61-3606) blocks antigen-induced airway inflammation in rodents. J Pharmacol Exp Ther 306:1174-1181
27. Hisamichi H, Naito R, Toyoshima A et al (2005) Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure-activity relationships of pyrimidine-5-carboxamide derivatives. Bioorg Med Chem 13:4936-4949
28. Rossi AB, Herlaar E, Braselmann S et al (2006) Identification of the Syk kinase inhibitor R112 by a human mast cell screen. J Allergy Clin Immunol 118:749-755
29. Meltzer EO, Berkowitz RB, Grosshead EB (2005) An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol 115:791-796
30. Braselman S, Taylor V, Zhao H et al (2006) R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 319:998-1008
31. Pine PR, Chang B, Schoettler N et al (2007) Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol 124:244-257
32. Kamens JS, Ratnofsky SE, Hirst GC et al (2001) Lck inhibitors as a therapeutic approach to autoimmune disease and transplant rejection. Curr Opin Investig Drugs 2:1213-1219
33. Bamborough P, Angell RM, Bhamra I et al (2007) N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: Indazoles as phenol isosteres with improved pharmacokinetics. Bioorg Med Chem Lett 17:4363-4368
34. Di Mauro EF, Newcomb J, Nunes JJ et al (2007) Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR. Bioorg Med Chem Lett 17:2305-2309
35. Martin MW, Newcomb J, Nunes JJ et al (2007) Discovery of novel 2,3-diarylfuro[2,3-b]pyridine-4-amines as potent and selective inhibitors of Lck: Synthesis, SAR, and pharmacokinetic properties. Bioorg Med Chem Lett 17:2299-2304
36. Abbott L, Betschmann P, Burchat A et al (2007) Discovery of thienopyridines as Src-family selective Lck inhibitors. Bioorg Med Chem Lett 17:1167-1171
37. Burchat A, Borhani DW, Calderwood DJ et al (2006) Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection. Bioorg Med Chem Lett 16:118-122
38. Mukaiyama H, Nishimura T, Kobayashi S et al (2007) Synthesis and c-Src inhibitory activity of imidazo[1,5-a]pyrazine derivatives as an agent for the treatment of acute ischemic stroke. Bioorg Med Chem 15:868-885
39. Noronha G, Barrett K, Boeccia A et al (2007) Discovery of [7-(2,6 -dichlorophenyl)-5-methylbenzo[1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1 -ylethoxy)phenyl]-amine - a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays. Bioorg Med Chem Lett 17:602-608
40. Sabat M, VanRens JC, Laufersweiler MJ et al (2006) The development of 2-benzimidazole substituted pyrimidine based inhibitors of lymphocyte specific kinase (Lck). Bioorg Med Chem Lett 16:5973-5977
41. Sabat M, VanRens JC, Brugel TA et al (2006) The development of novel 1,2-dihydro-pyrimido[4,5-c]pyridazine based inhibitors of lymphocyte specific kinase (Lck). Bioorg Med Chem Lett 16:4257-4261
42. Maier JA, Brugel TA, Sabat M et al (2006) Development of N-4,6-pyrimidine-N-alkyl-N'-phenyl ureas as orally active inhibitors of lymphocyte specific tyrosine kinase. Bioorg Med Chem Lett 16:3646-3650
43. Das J, Chen P, Norris D et al (2006) 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2- 6-[4-(2-hydroxyethyl)-1-pipe razinyl)]-2-methyl-4-pyrimidinyl]amino)]1,3-thiazole-5-carboxamide (dasatinib, BMS-345825) as a potent pan-Src kinase inhibitor. J Med Chem 49:6819-6832
44. DiMauro EF, Newcomb J, Nunes JJ et al (2006) Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. J Med Chem 49:5671-5686
45. Cetkovic-Cvrlje M, Tibbles HE (2004) Therapeutic potential of Janus kinase 3 (JAK3) inhibitors. Curr Pharm Des 10:1767-1784
46. Notarangelo LD, Giliani S, Mazza C et al (2000) Of genes and phenotypes: the immunological and molecular spectrum of combined immune deficiency. Defects of the γc-JAK3 signaling pathways as a model. Immunol Rev 178:39-48
47. Suzuki K, Nakajima H, Saito Y et al (2000) Janus kinase 3 (Jak3) is essential for common cytokine receptor γ chain (γc) -dependent signaling: Comparative analysis of γc, Jak3, and γc and Jak3 double-deficient mice. Int Immunol 12:123-132
48. Vassilev AO, Tibbles H, DuMez D et al (2006) Targeting JAK3 and BTK tyrosine kinases with rationally-designed inhibitors. Curr Drug Targets 7:327-343
49. Deuse T, Velotta JB, Hoyt G et al (2008) Novel immunosuppression: R348, a JAK3- and Syk-inhibitor attenuates acute cardiac allograft rejection. Transplantation 85:885-892
50. Changelian PS, Moshinsky D, Kuhn CF et al (2008) The specificity of JAK3 kinase inhibitors. Blood 111:2155-2157
51. Changelian PS, Flanagan ME, Ball DJ et al (2003) Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302:875-878
52. Kudlacz E, Perry B, Sawyer P et al (2004) The novel JAK3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models. Am J Transplant 4:51-57
53. Milici A, Kudlacz EM, Audoly L et al (2008) Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. Arthritis Res Ther 10:R14
54. Kremer JM, Bloom BJ, Breedveid FC et al (2006) A randomized, double-blind, placebo-controlled trial of 3 dose levels of CP-690,550 versus placebo in the treatment of active rheumatoid arthritis (abstract L40). Presented at the American College of Rheumatology Annual Meeting, November 2006, Washington DC
55. Busque S, Leventhal J, Brennan D et al (2007) CP-690,550 (CP), a JAK3 inhibitor, in de novo kidney transplant (KT) recipients: 6-month results of a phase 2 trial (abstract). Am J Transplant 2:304
56. Clark MP, George KM, Bookland RG et al (2007) Development of new pyrrolopyrimidine-based inhibitors of Janus kinase 3 (JAK3). Bioorg Med Chem Lett 17:1250-1253
57. Chen JJ, Thakur KD, Clark MP et al (2006) Development of pyrimidine-based inhibitors of Janus tyrosine kinase 3. Bioorg Med Chem Lett 17:5633-5638
58. Yang S-M, Malaviya R, Wilson LJ et al (2007) Simplified staurosporine analogs as potent JAK3 inhibitors. Bioorg Med Chem Lett 17:326-331