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The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer

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Pages 1893-1905 | Published online: 23 Oct 2009

Bibliography

  • Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal 2000;12:1-13
  • Yu L, Hébert MC, Zhang YE. TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses. EMBO J 2002;21:3749-59
  • Pearson G, Robinson F, Beers Gibson T, Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001;22:153-83
  • Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene 2007;26:3279-90
  • Schindler JF, Monahan JB, Smith WG. p38 pathway kinases as anti-inflammatory drug targets. J Dent Res 2007;86:800-11
  • Kaminska B. MAPK signalling pathways as molecular targets for anti-inflammatory therapy: from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 2005;1754:253-62
  • Lee JC, Laydon JT, McDonnell PC, A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994;372:739-46
  • Newton R, Holden N. Inhibitors of p38 mitogen-activated protein kinase: potential as anti-inflammatory agents in asthma? BioDrugs 2003;17:113-29
  • Hale KK, Trollinger D, Rihanek M, Manthey CL. Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages. J Immunol 1999;162:4246-52
  • Beardmore VA, Hinton HJ, Eftychi C, Generation and characterization of p38 beta (MAPK11) gene-targeted mice. Mol Cell Biol 2005;25:10454-64
  • Perregaux DG, Dean D, Cronan M, Inhibition of interleukin-1 beta production by SKF86002: evidence of two sites of in vitro activity and of a time and system dependence. Mol Pharmacol 1995;48:433-42
  • Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001;81:807-69
  • Raingeaud J, Gupta S, Rogers JS, Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 1995;270:7420-26
  • Sugden PH, Clerk A. Stress-responsive mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ Res 1998;83:345-52
  • Sweeney G, Somwar R, Ramlal T, An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes. J Biol Chem 1999;274:10071-8
  • Heidenreich KA, Kummer JL. Inhibition of p38 mitogen-activated protein kinase by insulin in cultured fetal neurons. J Biol Chem 1996;271:9891-4
  • Jiang Y, Gram H, Zhao M, Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. J Biol Chem 1997;272:30122-8
  • Hu MC, Wang YP, Mikhail A. Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines. J Biol Chem 1999;274:7095-102
  • Cuenda A, Cohen P, Buee-Scherrer V, Goedert M. Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). EMBO J 1997;16:295-305
  • Enslen H, Raingeaud J, Davis RJ. Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. J Biol Chem 1998;273:1741-8
  • Han J, Lee JD, Jiang Y, Characterization of the structure and function of a novel MAP kinase kinase (MKK6). J Biol Chem 1996;271:2886-91
  • Stein B, Brady H, Yang MX, Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade. J Biol Chem 1996; 271:11427-33
  • Moriguchi T, Kuroyanagi N, Yamaguchi K, A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem 1996;271:13675-9
  • Moriguchi T, Toyoshima F, Gotoh Y, Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase Kinase 6 by osmotic shock, tumor necrosis factor-? and H2O2 J Biol Chem 1996;271:26981-8
  • Yamauchi J, Tsujimoto G, Kaziro Y, Itoh H. Parallel regulation of mitogen-activated protein kinase kinase 3 (MKK3) and MKK6 in Gq-signaling cascade. J Biol Chem 2001;276:23362-72
  • Bagrodia S, Dérijard B, Davis RJ, Cerione RA. Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem 1995;270:27995-8
  • Zhang S, Han J, Sells MA, Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem 1995;270:23934-6
  • Kim MS, Lee EJ, Kim HR, Moon A. p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res 2003;63:5454-61
  • Nick JA, Avdi NJ, Young SK, Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP. J Clin Invest 1997;99:975-86
  • Zhang Y, Neo SY, Han J, RGS16 attenuates galphaq-dependent p38 mitogen-activated protein kinase activation by platelet-activating factor. J Biol Chem 1999;274:2851-7
  • Kotlyarov A, Neininger A, Schubert C, MAPKAP kinase 2 is essential for LPS-induced TNFalpha biosynthesis. Nat Cell Biol 1999;1:94-7
  • Hegen M, Gaestel M, Nickerson-Nutter CL, MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis. J Immunol 2006;177:1913-17
  • Ben-Levy R, Hooper S, Wilson R, Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. Curr Biol 1998;8:1049-57
  • Engel K, Kotlyarov A, Gaestel M. Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation. EMBO J 1998;17:3363-71
  • McLaughlin MM, Kumar S, McDonnell PC, Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. J Biol Chem 1996;271:8488-92
  • New L, Jiang Y, Zhao M, PRAK, a novel protein kinase regulated by the p38 MAP kinase. EMBO J 1998;17:3372-84
  • Zhu T, Lobie PE. Janus kinase 2-dependent activation of p38 mitogen-activated protein kinase by growth hormone: resultant transcriptional activation of ATF-2 and CHOP, cytoskeletal re-organization and mitogenesis. J Biol Chem 2000;275:2103-14
  • Han J, Jiang Y, Li Z, Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature 1997;386:296-9
  • Wang XZ, Ron D. Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase. Science 1996;272:1347-9
  • Yang SH, Galanis A, Sharrocks AD. Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors. Mol Cell Biol 1999;19:4028-37
  • Vermeulen L, De Wilde G, Van Damme P, Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J 2003;22:1313-24
  • Song H, Ki SH, Kim SG, Moon A. Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res 2006;66:10487-96
  • Carter AB, Knudtson KL, Monick MM, The p38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression. The role of TATA-binding protein (TBP). J Biol Chem 1999;274:30858-63
  • Campbell J, Ciesielski CJ, Hunt AE, A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B with implications for therapy in rheumatoid arthritis. J Immunol 2004;173:6928-37
  • Underwood DC, Osborn RR, Bochnowicz S, SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol 2000;279:L895-902
  • Pietersma A, Tilly BC, Gaestel M, p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level. Biochem Biophys Res Commun 1997;230:44-8
  • Craxton A, Shu G, Graves JD, p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes. J Immunol 1998;161:3225-36
  • Ridley SH, Sarsfield SJ, Lee JC, Actions of IL-1 are selectively controlled by p38 mitogenactivated protein kinase: regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels. J Immunol 1997;158:3165-73
  • Mbalaviele G, Anderson G, Jones A, Inhibition of p38 mitogen-activated protein kinase prevents inflammatory bone destruction. J Pharmacol Exp Ther 2006;317:1044-53
  • Barnes PJ. Novel signal transduction modulators for the treatment of airway diseases. Pharmacol Ther 2006;109:238-45
  • Haddad EB, Birrell M, McCluskie K, Role of p38 MAP kinase in LPS-induced airway inflammation in the rat. Br J Pharmacol 2001;132:1715-24
  • Escott KJ, Belvisi MG, Birrell MA, Effect of the p38 kinase inhibitor, SB 203580, on allergic airway inflammation in the rat. Br J Pharmacol 2000;131:173-6
  • Fujita M, Igarashi T, Kurai T, Correlation between dry eye and rheumatoid arthritis activity. Am J Ophthalmol 2005;140:808-13
  • Sweeney SE, Firestein GS. Signal transduction in rheumatoid arthritis. Curr Opin Rheumatol 2001;16:231-7
  • Kumar S, Blake SM, Emery JG. Intracellular signaling pathways as a target for the treatment of rheumatoid arthritis. Curr Opin Pharmacol 2001;1:307-13
  • Badger AM, Bradbeer JN, Votta B, Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock, and immune function. J Pharmacol Exp Ther 1996;279:1453-61
  • Jackson JR, Bolognese B, Hillegass L, Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models. J Pharmacol Exp Ther 1998;284:687-92
  • Badger AM, Griswold DE, Kapadia R, Disease-modifying activity of SB 242235, a selective inhibitor of p38 mitogen-activated protein kinase, in rat adjuvant-induced arthritis. Arthritis Rheum 2000;43:175-83
  • Wada Y, Nakajima-Yamada T, Yamada K, R-130823, a novel inhibitor of p38 MAPK, ameliorates hyperalgesia and swelling in arthritis models. Eur J Pharmacol 2005;506:285-95
  • Wadsworth SA, Cavender DE, Beers SA, RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. J Pharmacol Exp Ther 1999;291:680-7
  • Summers RW, Elliott DE, Qadir K, Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 2003;98:2034-41
  • Hollenbach E, Neumann M, Vieth M, Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J 2004;18:1550-2
  • Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001;2:734-44
  • McDonald DR, Bamberger ME, Combs CK, Landreth GE. Beta-amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes. J Neurosci 1998;18:4451-60
  • Legos JJ, Erhardt JA, White RF, SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia. Brain Res 2001;892:70-7
  • Barone FC, Irving EA, Ray AM, SB 239063, a second-generation p38 mitogen activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia. J Pharmacol Exp Ther 2001;296:312-21
  • Barone FC, Irving EA, Ray AM, Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Med Res Rev 2001;21:129-45
  • Koistinaho M, Kettunen MI, Goldsteins G, Beta-amyloid precursor protein transgenic mice that harbor diffuse A beta deposits but do not form plaques show increased ischemic vulnerability: role of inflammation. Proc Natl Acad Sci 2002;99:1610-5
  • Maroney AC, Finn JP, Connors TJ, Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem 2001;276:25302-8
  • Rust W, Kingsley K, Petnicki T, Heat shock protein 27 plays two distinct roles in controlling human breast cancer cell migration on laminin-5. Mol Cell Biol Res Commun 1999;1:196-02
  • Simon C, Simon M, Vucelic G, The p38 SAPK pathway regulates the expression of the MMP-9 collagenase via AP-1-dependent promoter activation. Exp Cell Res 2001;271:344-55
  • Nemoto T, Kubota S, Ishida H, Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors. World J Gastroenterol 2005;11:3065-9
  • Davidson B, Givant-Horwitz V, Lazarovici P, Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): co-expression in metastatic serous ovarian carcinoma. Clin Exp Metastasis 2003;20:621-31
  • Morooka T, Nishida E. Requirement of p38 mitogen-activated protein kinase for neuronal differentiation in PC12 cells. J Biol Chem 1998;273:24285-8
  • Junttila MR, Ala-Aho R, Jokilehto T, p38alpha and p38delta mitogen-activated protein kinase isoforms regulate invasion and growth of head and neck squamous carcinoma cells. Oncogene 2007;26:5267-79
  • Lim SJ, Lee YJ, Lee E. p38MAPK inhibitor SB203580 sensitizes human SNU-C4 colon cancer cells to exisulind-induced apoptosis. Oncol Rep 2006;16:1131-5
  • Guo X, Ma N, Wang J, Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells. BMC Cancer 2008;8:375
  • Yasui H, Hideshima T, Ikeda H, BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (HSP) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/HSP27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth. Br J Haematol 2007;136:414-23
  • Shin I, Kim S, Song H, H-Ras-specific activation of Rac-MKK3/6-p38 pathway: its critical role in invasion and migration of breast epithelial cells. J Biol Chem 2005; 280: 14675-83
  • Tryggvason K. Type IV collagenase in invasive tumors. Breast Cancer Res 1993;24:209-18
  • Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991;64:327-36
  • Xu L, Chen S, Bergan RC. MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer. Oncogene 2006;25:2987-98
  • Denkert C, Siegert A, Leclere A, An inhibitor of stress-activated MAP-kinases reduces invasion and MMP-2 expression of malignant melanoma cells. Clin Exp Metastasis 2002;19:79-85
  • Johansson N, Ala-aho R, Uitto V, Expression of collagenase-3 (MMP-13) and collagenase-1 (MMP-1) by transformed keratinocytes is dependent on the activity of p38 mitogen-activated protein kinase. J Cell Sci 2000;113:227-35
  • Han YC, Zeng XX, Wang R, Correlation of p38 mitogen-activated protein kinase signal transduction pathway to uPA expression in breast cancer. Ai Zheng 2007;26:48-53
  • Zhou HY, Pon YL, Wong AS. Synergistic effects of epidermal growth factor and hepatocyte growth factor on human ovarian cancer cell invasion and migration: role of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Endocrinology 2007;148:5195-208
  • Simon C, Goepfert H, Boyd D. Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Res 1998;58:1135-9
  • Yao J, Xiong S, Klos K, Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells. Oncogene 2001;20:8066-74
  • She QB, Chen N, Dong Z. ERKs and p38 kinase phosphorylate p53 protein at serine 15 in response to UV radiation. J Biol Chem 2000;275:20444-9
  • She QB, Bode AM, Ma WY, Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res 2001;61:1604-10
  • Bradham C, McClay DR. p38 MAPK in development and cancer. Cell Cycle 2006;5:824-8
  • Iyoda K, Sasaki Y, Horimoto M, Involvement of the p38 mitogen-activated protein kinase cascade in hepatocellular carcinoma. Cancer 2003;97:3017-26
  • Corrèze C, Blondeau JP, Pomérance M. p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells. Eur J Endocrinol 2005;153:123-33
  • Chang HL, Wu YC, Su JH, Protoapigenone, a novel flavonoid, induces apoptosis in human prostate cancer cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase 1/2. J Pharmacol Exp Ther 2008;325:841-9
  • Croons V, Martinet W, Herman AG, The protein synthesis inhibitor anisomycin induces macrophage apoptosis in rabbit atherosclerotic plaques through p38 mitogen-activated protein kinase. J Pharmacol Exp Ther 2009;329:856-64
  • Elenitoba-Johnson KS, Jenson SD, Abbott RT, Involvement of multiple signaling pathways in follicular lymphoma transformation: p38-mitogen-activated protein kinase as a target for therapy. Proc Natl Acad Sci U S A 2003;100:7259-64
  • Karahashi H, Nagata K, Ishii K, Amano F. A selective inhibitor of p38 MAP kinase, SB202190, induced apoptotic cell death of a lipopolysaccharide-treated macrophage-like cell line, J774.1. Biochem Biophys Acta 2000;1502:207-23
  • Navas TA, Nguyen AN, Hideshima T, Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo. Leukemia 2006;20:1017-27
  • Lantos I, Bender PE, Razgaitis KA, Antiinflammatory activity of 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazoles. Isomeric 4-pyridyl and 4-substituted phenyl derivatives. J Med Chem 1984;27:72-5
  • Saccani S, Pantano S, Natoli G. p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat Immunol 2002;3:69-75
  • Pargellis C, Tong L, Churchill L, Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat Struct Biol 2002;9:268-72
  • Karaman MW, Herrgard S, Treiber DK, A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008;26:127-32
  • Fabian MA, Biggs WH, Treiber DK, A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 2005;23:329-36
  • Zack D, Campagnuolo GS, Middleton S, 66th American College of Rheumatology Annual Scientific Meeting, Orlando, 2003. J Clin Rheumatol 2002;8:207
  • Boehringer Ingelheim Pharmaceuticals Inc. Method for administering BIRB 796 BS. WO/2003/049742; 2003
  • Hill RJ, Dabbagh K, Phippard D, Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity. J Pharmacol Exp Ther 2008;327:610-9
  • Kim ES, Kim MS, Moon A. Transforming growth factor (TGF)-beta in conjunction with H-ras activation promotes malignant progression of MCF10A breast epithelial cells. Cytokine 2005;21(29):84-91
  • Kim ES, Kim MS, Moon A. TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. Int J Oncol 2004;25:1375-82
  • Kim ES, Sohn YW, Moon A. TGF-beta-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF)2 in human breast epithelial cells. Cancer Lett 2007;252:147-56
  • Song H, Moon A. Glial cell-derived neurotrophic factor (GDNF) promotes low-grade Hs683 glioma cell migration through JNK, ERK-1/2 and p38 MAPK signaling pathways. Neurosci Res 2006;56:29-38
  • Dominguez C, Powers DA, Tamayo N. p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel 2005;8:421-30
  • Lee MR, Dominguez C. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. Curr Med Chem 2005;12:2979-94
  • Mongin-Bulewski C. Drug Discovery Technology 2002 (Part V) - Overnight Report. Boston MA, USA. IDdb Meeting Report. 4-9 August 2002
  • Gruenbaum LM, Schwartz R, Woska JR, Inhibition of pro-inflammatory cytokine production by the dual p38/JNK2 inhibitor BIRB796 correlates with the inhibition of p38 signaling. Biochem Pharmacol 2009;77:422-32
  • Branger J, van den Blink B, Weijer S, Inhibition of coagulation, fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor during human endotoxemia. Blood 2003;101:4446-8
  • Schreiber S, Feagan B, D'Haens G, Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006;4:325-34
  • Cohen SB, Cheng TT, Chindalore V, Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum 2009;60:335-44
  • Alten RE, Zerbini C, Jeka S, Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy. Ann Rheum Dis 2009: published online 8 Apr 2009, doi:10.1136/ard.2008.104802
  • Pusztai L, Mendoza TR, Reuben JM, at al. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine 2004;25:94-102
  • Fijen JW, Zijlstra JG, De Boer P, Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers. Clin Exp Immunol 2001;124:16-20
  • Behr TM, Berova M, Doe CP, p38 mitogen-activated protein kinase inhibitors for the treatment of chronic cardiovascular disease. Curr Opin Investig Drugs 2003;4:1059-64
  • Braddock M. Inflammation in drug discovery and development SRI's seventh international meeting. San Diego, CA, USA. IDdb Meeting Report. 20-21 February 2003
  • GlaxoSmithKline. P38 mitogen-activated protein (MAP) kinase inhibitor (SB681323) study in patients with neuropathic pain. ClinicalTrials.gov, Bethesda, MD: National Library of Medicine. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00390845 [Last accessed May 2009]
  • GlaxoSmithKline Product development pipeline. GlaxoSmithKline Inc. February 2009. Available from: www.gsk.com/investors/pp_pipeline_standard.htm [Last accessed May 2005]
  • Pargellis C, Regan J. Inhibitors of p38 mitogen-activated protein kinase for the treatment of rheumatoid arthritis. Curr Opin Investig Drugs 2003;4:566-71
  • Tong MD, Daniels DO, Montano T, SCIO-469, a novel p38A MAPK inhibitor, provides efficacy in acute postsurgical dental pain. Clin Pharm Ther 2004;75:3
  • Genovese MC, Cohen SB, Wofsy D, A randomized, double-blind, placebo-controlled phase 2 study of an oral p38 alpha MAPK inhibitor, SCIO-469, in patients with active rheumatoid arthritis. San Francisco: 72th American College of Rheumatology Annual Scientific Meeting, 24-29 October 2008
  • Fitzgerald CE, Patel SB, Becker JW, Structural basis for p38? MAP kinase quinazoline and pyridol-pyrimidine inhibitor specificity Nat Struct Biol 2003;10:764-69
  • Weisman M, Furst D, Schiff M, A double-blind, placebo controlled trial of VX-745, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor in patients with rheumatoid arthritis(RA). FRI0018. Stockholm: European League Against Rheumatism, Annual Congress, Jun 12-15, 2002
  • Vertex Pharmaceuticals Inc. Vertex moves to re-allocate resources from VX-745 in p38MAP kinase program to accelerate development of second generation drug candidates VX-702 and VX-850. Press Release 2001
  • Vertex Pharmaceuticals Inc. Preliminary Phase IIa data for VX-702 demonstrate tolerability and reduction in C-reactive protein in cardiovascular patients. Rome: European Society of Cardiology's Acute Cardiac Care Symposium, 17-20 October 2004
  • Damjanov N, Kauffman R, Spencer-Green GT. Safety and efficacy of VX-702, a p38 MAP kinase inhibitor, in rheumatoid arthritis. OP-0246. Paris: European League Against Rheumatism, Annual Congress, Jun 11-14, 2008
  • Damjanov N, Kauffman R, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: Results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum 2009;60:1232-41
  • Wang Y, Singh R, Lefkowitch JH, Tumor necrosis factor-induced toxic liver injury results from JNK2 dependent activation of caspase-8 and the mitochondrialdeath pathway. J Biol Chem 2006;281:15258-67
  • Muniyappa H, Das KC. Activation of c-Jun N-terminal kinase (JNK) by widely used specific p38 MAPK inhibitors SB202190 and SB203580: a MLK-3-MKK7-dependent mechanism. Cell Signal 2008;20:675-83
  • Heinrichsdorff J, Luedde T, Perdiguero E, p38alpha MAPK inhibits JNK activation and collaborates with IkappaB kinase 2 to prevent endotoxin-induced liver failure. EMBO Rep 2008;9:1048-54
  • Whitmarsh AJ, Yang SH, Su MS, Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors. Mol Cell Biol 1997;17:2360-71
  • Brancho D, Tanaka N, Jaeschke A, Mechanism of p38 MAP kinase activation in vivo. Genes Dev 2003;17:1969-78
  • Ventura JJ, Tenbaum S, Perdiguero E, p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet 2007;39:750-8
  • Gaestel M, Kotlyarov A, Kracht M. Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov 2009;8:480-99
  • Ronkina N, Kotlyarov A, Dittrich-Breiholz O, The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK. Mol Cell Biol 2007;27:170-81
  • Ananieva O, Darragh J, Johansen C, The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling. Nat Immunol 2008;9:1028-36
  • Brook M, Tchen CR, Santalucia T, Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways. Mol Cell Biol 2006;26:2408-18
  • Cohen P. Targeting protein kinases for the development of anti-inflammatory drugs. Curr Opin Cell Biol 2009;21:317-24
  • Mayer RJ, Callahan JF. p38 MAP kinase inhibitors: a future therapy for inflammatory diseases. Drug Discov Today 2006;3:49-54

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