RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase

Journal of Pharmacology and Experimental Therapeutics

Volumn 291, Issue 2, 1999, Pages 680-687

  Wadsworth, Scott A ^a   Cavender, Druie E ^a   Beers, Scott A ^a   Lalan, Praful ^a   Schafer, Peter H ^a   Malloy, Elizabeth A ^a   Wu, Wei ^a   Fahmy, Bohumila ^a   Olini, Gilbert C ^a   Davis, Janet E ^a   Pellegrino Gensey, J Lee ^a   Wachter, Michael P ^a   Siekierka, John J ^a  

^a Drug Discovery Raritan   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 [4 (4 FLUOROPHENYL) 1 (3 PHENYLPROPYL) 5 (4 PYRIDINYL) 1H IMIDAZOL 2 YL] 3 BUTYN 1 OL; CYCLOOXYGENASE 1; ENTEROTOXIN; GAMMA INTERFERON; INTERLEUKIN 1BETA; INTERLEUKIN 2; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN TYROSINE KINASE; STAPHYLOCOCCUS TOXIN; SUPERANTIGEN; THROMBOXANE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; HUMAN TISSUE; LYMPHOCYTE PROLIFERATION; MALE; NONHUMAN; NORMAL HUMAN; PRIORITY JOURNAL; RAT; T LYMPHOCYTE;

ANIMALS; ANTIGENS; CELL DIVISION; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; ENTEROTOXINS; ENZYME INHIBITORS; HUMANS; IMIDAZOLES; INTERFERON TYPE II; INTERLEUKIN-2; LIPOPOLYSACCHARIDES; MACROPHAGES; MALE; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; MONOCYTES; PROTEIN KINASES; PYRIDINES; RATS; RATS, INBRED LEW; STAPHYLOCOCCUS; T-LYMPHOCYTES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0032745423     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (31)

1. Badger AM, Bradbeer JN, Votta B, Lee JC, Adams JL and Griswold DE (1996) 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 279:1453-1461.
2. Badger AM, Cook MN, Lark MW, Newman-Tarr TM, Swift BA, Nelson AH, Barone FC and Kumar S (1998) SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. J Immunol 161:467-473.
3. Baldassare JJ, Bi Y and Bellone CJ (1999) The role of p38 mitogen-activated protein kinase in IL-1β transcription. J Immunol 162:5367-5373.
4. Borsch-Haubold AG, Pasquet S and Watson SP (1998) Direct inhibition of cyclooxygenase-1 and -2 by the kinase inhibitors SB 203580 and PD 98059: SB 203580 also inhibits thromboxane synthase. J Biol Chem 273:28766-28772.
5. Cain BS, Meldrum DR, Meng X, Dinarello CA, Shames BD, Banerjee A and Harken AH (1999) p38 MAPK inhibition decreases TNF-α production and enhances post-ischemic human myocardial function. J Surg Res 83:7-12.
6. Cohen PS, Schmidtmayerova H, Dennis J, Dubrovsky L, Sherry B, Wang H, Bukrinsky M and Tracey KJ (1997) The critical role of p38 MAP kinase in T cell HIV-1 replication. Mol Med 3:339-346.
7. Crawley JB, Rawlinson L, Lali FV, Page TH, Saklatvala J and Foxwell BMJ (1997) T cell proliferation in response to interleukins 2 and 7 requires p38 MAP kinase activation. J Biol Chem 272:15023-15027.
8. Cuenda A, Rouae J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR and Lee JC (1995) SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 364:229-233.
9. Dean JLE, Brook M, Clark AR and Saklatvala J (1999) p38 mitogen-activated protein kinase regulates cyclooxygenase-2 mRNA stability and transcription in lipopolysaccharide-treated human monocytes. J Biol Chem 274:264-269.
10. Dinarello CA (1991) Inflammatory cytokines: Interleukin-1 and tumor necrosis factor as effector molecules in autoimmune disease. Curr Opin Immunol 3:941-948.
11. Frantz B, Klatt T, Pang M, Parsons J, Rolando A, Williams H, Tocci MJ, O'Keefe SJ and O'Neill EA (1998) The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding. Biochemistry 37:13846-13853.
12. Griswold DE and Young PR (1996) Pharmacology of cytokine suppressive anti-inflammatory drug binding protein (CSBP), a novel stress-induced kinase. Pharmacol Commun 7:323-329.
13. Gum RJ, McLaughlin MM, Kumar S, Wang Z, Bower MJ, Lee JC, Adams JL, Livi GP, Goldsmith EJ and Young PR (1998) Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket. J Biol Chem 273:15605-15610.
14. Jackson JR, Bolognese B, Hillegass L, Shouki K, Adams J, Griswold DE and Winkler JD (1998) Pharmacological effects of SB220025, a selective inhibitor of p38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models. J Pharmacol Exp Ther 284:687-692.
15. Koprak S, Staruch MJ and Dumont FJ (1999) A specific inhibitor of the p38 mitogen activated protein kinase affects differentially the production of various cytokines by activated human T cells: Dependence on CD28 signaling and preferential inhibition of IL-10 production. Cell Immunol 192:87-95.
16. Kumar S, McDonnell PC, Gum RJ, Hand AT, Lee JC and Young PR (1997) Novel homologues of CSBP/p38 MAP kinase: Activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochem Biophys Res Commun 235: 533-538.
17. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, Strickler JE, McLaughlin MM, Siemens IR, Fisher SM, Livi GP, White JR, Adams JL and Young PR (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature (Lond) 372:739-746.
18. Lisnock JM, Tebben A, Frantz B, O'Neill EA, Croft G, O'Keefe SJ, Li B, Hacker C, de Laszlo S, Smith A, Libby B, Liverton N, Hermes J and LoGrasso P (1998) Molecular basis for p38 protein kinase inhibitor specificity. Biochemistry 37:16573-16581.
19. Lu H-T, Yang DD, Wysk M, Gatti E, Mellman I, Davis RJ and Flavell RA (1999) Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice. EMBO J 18:1845-1857.
20. Ma XL, Kumar S, Gao F, Louden CS, Lopez BL, Christopher TA, Wang C, Lee JC, Feuerstein GZ and Yue T-L (1999) Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 99:1685-1691.
21. Martin M and Resch K (1988) Interleukin-1: More than a mediator between leukocytes. Trends Pharmacol Sci 9:171-177.
22. Nagata Y, Moriguchi T, Nishida E and Todokoro K (1997) Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3. Blood 90:929-934.
23. Nemeth E, Bole-Feysot C and Tashima LS (1998) Suppression subtractive hybridization (SSH) identifies prolactin stimulation of p38 MAP kinase gene expression in Nb2 T lymphoma cells: Molecular cloning of rat p38 MAP kinase. J Mol Endocrinol 20:151-156.
24. Ridley SH, Sarsfield SJ, Lee JC, Bigg HF, Cawston TE, Taylor DJ, DeWitt DL, and Saklatvala J (1997) Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase. J Immunol 158:3165-3173.
25. Rincon M, Enslen H, Raingeaud J, Recht M, Zapton T, Su MS-S, Penix LA, Davis RJ, and Flavell RA (1998) Interferon-γ expression by Th1 effector T cells mediated by the p38 MAP kinase signaling pathway. EMBO J 17:2817-2829.
26. + T cells and Th2 effector cells. J Immunol 162:7110-7119.
27. Schafer PH, Wang L, Wadsworth SA, Davis JE and Siekierka JJ (1999b) T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-α production in a manner distinct from LPS activation of monocytes. J Immunol 162:659-668.
28. Shapiro L, Heidenreich KA, Meintzer MK and Dinarello CA (1998) Role of p38 mitogen-activated protein kinase in HIV type I production in vitro. Proc Natl Acad Sci USA 95:7422-7426.
29. Tong L, Pav S, White DM, Rogers S, Crane KM, Cywin CL, Brown ML and Pargellis CA (1997) A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket. Nat Struct Biol 4:311-316.
30. Wilson KP, McCaffrey PG, Hsiao K, Pazhanisamy S, Galullo V, Bemis GW, Fitzgibbon MJ, Caron PR, Murcko MA and Su MSS (1997) The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase. Chem Biol 4:423-431.
31. Zu Y-L, Qi J, Gilchrist A, Fernandez GA, Vazquez-Abad D, Kreutzer DL, Huang C-K and Sha'afi RI (1998) p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-α or FMLP stimulation. J Immunol 160:1982-1989.