GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo

British Journal of Pharmacology

Volumn 145, Issue 3, 2005, Pages 301-312

  Alderton, Wendy K ^a,d   Angell, Anthony D R ^a   Craig, Caroline ^a   Dawson, John ^a   Garvey, Edward ^b   Moncada, Salvador ^c   Monkhouse, Jayne ^c,e   Rees, Daryl ^c,f   Russell, Linda J ^a   Russell, Rachel J ^a,g   Schwartz, Sheila ^a   Waslidge, Neil ^a   Knowles, Richard G ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d PIramed Ltd   (United Kingdom)

^e ROCHE PRODUCTS LTD   (United Kingdom)

^f Phytopharm plc   (United Kingdom)

^g PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

GW273629; GW274150; Nitric oxide synthase; NOS II; NOS2

Indexed keywords

3 [[2 [(1 IMINOETHYL)AMINO]ETHYL]SULFONYL]ALANINE; GW 273629; INDUCIBLE NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; S [2 (1 IMINOETHYLAMINO)ETHYL]HOMOCYSTEINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BLOOD PRESSURE REGULATION; CEREBELLUM; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; STEADY STATE; TIME;

ANIMALS; CELL LINE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HUMANS; MALE; MICE; RATS; RATS, WISTAR; SPODOPTERA; SULFIDES; SULFONES;

EID: 21244458471     PISSN: 00071188     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.bjp.0706168     Document Type: Article

References (35)

1. ALDERTON, W., ANGELL, A., CLAYTON, N., CRAIG, C., DAWSON, J., PREND, A., MCGILL, J., MANGEL, A., MONCADA, S., REES, D., RUSSELL, L., SCHWARTZ, S., WASLIDGE, N. & KNOWLES, R. (2000). GW274150 is a potent, long-acting, highly selective inhibitor of inducible nitric oxide synthase with therapeutic potential in post-operative ileus. In: Biology of Nitric Oxide, vol. 7, ed. Moncada, S., Gustafsson, L.E., Wiklund, N.P., & Higgs, E.A., pp. 22, London: Portland Press.
2. ALDERTON, W.K., COOPER, C.C. & KNOWLES, R.G. (2001). Nitric oxide synthases: structure, function and inhibition. Biochem. J., 357, 593-615.
3. 6-(1-iminoethyl)- lysine. Biochemistry, 37, 4844-4852.
4. CHARLES, I.G., SCORER, C.A., MORO, M.A., FERNANDEZ, C., CHUBB, A., DAWSON, J., FOXWELL, N., KNOWLES, R.G. & BAYLIS, S.A. (1996). Expression of human nitric oxide synthase isozymes. Methods Enzymol., 268, 449-460.
5. CHATTERJEE, P.K., PATEL, N.S., SIVARAJAH, A., KVALE, E.O., DUGO, L., CUZZOCREA, S., BROWN, P.A., STEWART, K.N., MOTA-FILIPE, H., BRITTI, D., YAQOOB, M.M. & THIEMERMANN, C. (2003). GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int., 63, 853-865.
6. CUZZOCREA, S., CHATTERJEE, P.K., MAZZON, E., MCDONALD, M.C., DUGO, L., DI PAOLA, R., SERRAINO, I., BRITTI, D., CAPUTI, A.P. & THIEMERMANN, C. (2002). Beneficial effects of GW274150, a novel, potent and selective inhibitor of iNOS activity, in a rodent model of collagen-induced arthritis. Eur. J. Pharmacol., 453, 119-129.
7. DAWSON, J. & KNOWLES, R.G. (1998). A microtitre plate assay of human NOS isoforms. In: Meth. Molec. Biol. 100, Nitric Oxide Protocols, ed. Titheradge, M.A. pp. 237-242. Totowa NJ: Humana Press.
8. DUGO, L., MARZOCCO, S., MAZZON, E., DI PAOLO, R., GENOVESE, T., CAPUTI, A.P. & CUZZOCREA, S. (2004). Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. Br. J. Pharmacol., 141, 979-987.
9. EVANS, S.M. & WHITTLE, B.J. (2003). Role of bacteria and inducible nitric oxide synthase activity in the systemic inflammatory microvascular response provoked by indomethacin in the rat. Eur. J. Pharmacol., 461, 63-71.
10. FOLKERTS, G., KLOEK, J., MUIJSERS, R.B.R. & NIJKAMP, P.P. (2001). Reactive nitrogen and oxygen species in airway inflammation. Eur. J. Pharmacol., 429, 251-262.
11. FOSETTA, J.D., NIU, X.D., LUNN, C.A., ZAVODNY, P.J., NARULA, S.K. & LUNDELL, D. (1996). Expression of human inducible nitric oxide synthase in Escherichia coli. FEBS Lett., 379, 135-138.
12. GARVEY, E.P., OPLINGER, J.A., FURFINE, E.S., KIFF, R.J., LASZLO, F., WHITTLE, B.J.R. & KNOWLES, R.G. (1997). 1400W is a slow-, tight-binding and highly selective inhibitor of inducible nitric oxide synthase in vitro and in vivo. J. Biol. Chem., 272, 4959-4963.
13. GARVEY, E.P., OPLINGER, J.A., TANOURY, G.J., SHERMANN, P.A., FOWLER, M., MARSHALL, S., HARMON, M.F., PAITH, J.E. & FURFINE, E.S. (1994). Potent and selective inhibition of human nitric oxide synthases. J. Biol. Chem., 269, 26669-26676.
14. HOBBS, A.J., HIGGS, A. & MONCADA, S. (1999). Inhibition of nitric oxide synthase as a potential therapeutic target. Ann. Rev. Pharmacol. Toxicol., 39, 191-220.
15. KOJIMA, H., NAKATSUBO, N., KIKUCHI, K., KAWAHARA, S., KIRINO, Y., NAGOSHI, H., HIRATA, Y. & NAGANO, T. (1998). Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal. Chem., 70, 2446-2453.
16. KNOWLES, R., DAWSON, J., WASLIDGE, N., RUSSELL, R., ANGELL, A., CRAIG, C., SCHWARTZ, S., EVANS, S., WHITTLE, B., GARVEY, E., MONKHOUSE, J., MONCADA, S. & REES, D. (2000). GW273629 is a highly-selective, short-acting iNOS inhibitor both in vitro and in vivo; beneficial effects in endotoxin shock. In: Biology of Nitric Oxide, Vol. 7, ed. Moncada, S., Gustafsson, L. E., Wiklund, N. P, & Higgs, E. A., pp. 21, London: Portland Press.
17. KNOWLES, R.G. & MONCADA, S. (1994). Nitric oxide synthases in mammals. Biochem. J., 298, 249-258.
18. LENTNER, C. (ed) (1984). Geigy Scientific Tables. Vol. 3, Composition of Blood. Basle, Switzerland: International Medical and Pharmaceutical Information, Ciba Geigy Limited.
19. LIZASOAIN, I., KNOWLES, R.G. & MONCADA, S. (1995). Inhibition by Lamotrigine of the generation of nitric oxide in rat forebrain slices. J. Neurochem., 64, 636-642.
20. MCCALL, T.B., FEELISCH, M., PALMER, R.M. & MONCADA, S. (1991). Identification of N-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. Br. J. Pharmacol., 102, 234-238.
21. MCDONALD, M.C., IZUMI, M., CUZZOCREA, S. & THIEMERMANN, C. (2002). A novel, potent and selective inhibitor of the activity of inducible nitric oxide synthase (GW274150) reduces the organ injury in hemorrhagic shock. J. Physiol. Pharmacol., 53, 555-569.
22. MONCADA, S. & HIGGS, E.A. (1995). Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J., 9, 1319-1330.
23. 6-(1-iminethyl)lysine: a selective inhibitor of inducible nitric oxide synthase. J Med. Chem., 37, 3886-3888.
24. MORRISON, J.F. & WALSH, C.T. (1988). The behaviour and significance of slow-binding enzyme inhibitors. Adv. Enzymol. Relat. Areas Mol. Biol., 61, 201-301.
25. REES, D.D., MONKHOUSE, J.E., CAMBRIDGE, D. & MONCADA, S. (1998). Nitric oxide and the haemodynamic profile of endotoxin shock in the conscious mouse. Br. J. Pharmacol., 124, 540-546.
26. RODEBERG, D.A., CHAET, M.S., BASS, R.C., ARKOVITZ, M.S. & GARCIA, V.F. (1995). Nitric oxide: an overview. Am. J. Surg., 170, 292-303.
27. RODRIGEUZ-CRESPO, I. & ORITZ de MONTELLANO, P.R. (1996). Human endothelial nitric oxide synthase: expression in Escherichia coli. Arch. Biochem. Biophys., 336, 151-156.
28. RUSSELL, R.J. (1998). Use of arginine analogs as inhibitors of nitric oxide synthase in rat aortic rings. In: Methods in Molecular Biology, Vol. 100, Nitric Oxide Protocols ed. Titheradge, M.A., pp. 243-250. Totowa, New Jersey: Humana Press.
29. SALTER, M., DUFFY, C., GARTHWAITE, J. & STRIJBOS, P.J.L.M. (1996). Ex vivo measurement of brain tissue nitrite and nitrate accurately reflects nitric oxide synthase activity in vivo. J. Neurochem., 66, 1683-1690.
30. 2+)-independent nitric oxide synthases. FEBS Lett., 291, 145-149.
31. VALLANCE, P. & LEIPER, J. (2002). Blocking NO synthesis: how, where and why? Nat. Rev. Drug Disc., 1, 939-950.
32. +) when the Griess reaction is used to assay for nitrite. Anal. Biochem., 224, 502-508.
33. WHITTLE, B.J. (1997). Nitric oxide: a mediator of inflammation or mucosal defence. Eur. J. Gastroenterol. Hepatol., 9, 1026-1032.
34. 6-iminoethyl-L-lysine and N5-iminoethyl-L-ornithine. Eur. J. Pharmacol., 350, 325-334.
35. YOUNG, R.J., BEAMS, R.M., CARTER, K., CLARK, H.A., COE, D.M., CHAMBERS, C.L., DAVIES, P.I., DAWSON, J., DRYSDALE, M.J., FRANZMAN, K.W., FRENCH, C., HODGSON, S.T., HODSON, H.F., KLEANTHOUS, S., RIDER, P., SANDERS, D., SAWYER, D.A., SCOTT, K.J., SHEARER, B.G., STOCKER, R., SMITH, S., TACKLEY, M.C. & KNOWLES, R.G. (2000). Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine. Bioorg. Med. Chem. Lett., 10, 597-600.