In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitor

Journal of Pharmacology and Experimental Therapeutics

Volumn 337, Issue 1, 2011, Pages 137-144

  Nials, Anthony T ^a   Tralau Stewart, Cathy J ^b   Gascoigne, Michele H ^a   Ball, Douglas I ^a   Ranshaw, Lisa E ^a   Knowles, Richard G ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CILOMILAST; FLUTICASONE PROPIONATE; GSK 256066; NITRIC OXIDE; ROFLUMILAST;

ACUTE DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; FERRET; IN VIVO STUDY; LOEFFLER PNEUMONIA; LUNG DISEASE; MALE; NONHUMAN; PNEUMONIA; PRIORITY JOURNAL; PULMONARY NEUTROPHILIA; RAT; VOMITING;

ADMINISTRATION, INHALATION; AMINOQUINOLINES; ANIMALS; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; EOSINOPHILIA; FERRETS; MALE; PHOSPHODIESTERASE 4 INHIBITORS; RATS; RATS, INBRED BN; RATS, SPRAGUE-DAWLEY; SULFONES;

EID: 79953012235     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.173641     Document Type: Article

References (33)

1. Bebo B, Kuss H, Hoppmann J, Hofgen N, and Rundfeldt C (2007) ELB526, a new selective PDE4 inhibitor with a large safety margin and potent activity in animal models of asthma. Am J Resp Crit Care 175:A690.
2. Birrell MA, McCluskie K, Hardaker E, Knowles R, and Belvisi MG (2006) Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model. Eur Respir J 28:1236-1244. (Pubitemid 44883862)
3. Birrell MA, McCluskie K, Wong S, Donnelly LE, Barnes PJ, and Belvisi MG (2005) Resevatrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-κB- independent mechanism. FASEB J 19:840-841. (Pubitemid 40617402)
4. Boswell-Smith V and Page CP (2006) Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of respiratory disease. Expert Opin Investig Drugs 15:1105-1113. (Pubitemid 44314661)
5. Bundschuh DS, Eltze M, Barsig J, Wollin L, Hatzelmann A, and Beume R (2001) In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J Pharmacol Exp Ther 297:280-290.
6. Calverley PM, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, and Fabbri LM (2007) Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Crit Care Med 176:154-161. (Pubitemid 47057851)
7. Chapman RW, House A, Jones H, Richard J, Celly C, Prelusky D, Ting P, Hunter JC, Lamca J, and Phillips JE (2007) Effect of inhaled roflumilast on the prevention and resolution of allergen-induced late-phase airflow obstruction in Brown Norway rats. Eur J Pharmacol 571:215-221. (Pubitemid 47385896)
8. Chapman RW, House A, Richard J, Prelusky D, Lamca J, Wang P, Lundell D, Wu P, Ting PC, Lee JF, et al. (2010) Pharmacology of a potent and selective inhibitor of PDE4 for inhaled administration. Eur J Pharmacol 643:274-281.
9. Christie P (2005) Roflumilast: a selective phosphodiesterase 4 inhibitor. Drugs Today 41:667-675.
10. Daguès N, Pawlowski V, Guigon G, Ledieu D, Sobry C, Hanton G, Freslon JL, and Chevalier S (2007) Altered gene expression in rat mesenteric tissue following in vivo exposure to phosphodiesterase 4 inhibitors. Toxicol Appl Pharmacol 218:52-63. (Pubitemid 46026843)
11. Dale TJ, Ball DI, Nials AT, and Coleman RA (1995) The anti-inflammatory and emetogenic properties of phosphodiesterase (PDE) inhibitors in conscious ferrets. Br J Pharmacol 116:91.
12. Deng YM, Xie QM, Tang HF, Sun JG, Deng JF, Chen JQ, and Yang SY (2006) Effects of ciclamilast, a new PDE4 inhibitor, on airway hyperresponsiveness, PDE4D expression and airway inflammation in a murine model of asthma. Eur J Pharmacol 547:125-135.
13. Djukanović R, Roche WR, Wilson JW, Beasley CR, Twentyman OP, Howarth RH, and Holgate ST (1990) Mucosal inflammation in asthma. Am Rev Respir Dis 142:434-457. (Pubitemid 20235959)
14. Ferreira IM, Hazari MS, Gutierrez C, Zamel N, and Chapman KR (2001) Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled budesonide. . Am J Resp Crit Care Med 164:1012-1015. (Pubitemid 32971650)
15. Fitzgerald MF, Briggs B.A, Thompson AM, Edwards DF, and Sturton RG (2001) The evaluation of a selective phosphodiesterase (PDE) 4 inhibitor, Bay 19-8004, in guinea-pig antigen challenge and ferret emesis models. Eur Respir J 18(Suppl 33):36.
16. Fregonese L, Grootendorst DC, Gaum SA, Wei CG, Bennetts M, Ward JK, Phillips PG, and Rabe KF (2007) The inhaled PDE4 inhibitor Tofimilast does not inhibit airway responses to allergen and histamine. Am J Resp Crit Care 175:A486.
17. Giembycz MA (2001) Cilomilast: a second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs 10:1361-1379.
18. Giembycz MA (2008) Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking? Br J Pharmacol 155:288-290.
19. Higgs G (2010) Is PDE4 too difficult a drug target? Curr Opin Invest Drugs 11:495-498.
20. Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, and Barnes PJ (1994) Increased nitric oxide in exhaled air of asthmatic patients. Lancet 343:133-155.
21. Knowles R, Ball D, Gascoigne M, Tralau-Stewart C, and Nials (2009a) In vivo characterization of GSK256066, an exceptionally high affinity and selective PDE4 inhibitor suitable for topical administration. Am J Rev Crit Care Med 179:A4582.
22. Knowles RG, Tralau-Stewart C, Dawson J, Hart GJ, Angell ADR, Solanke YE, Lucas FS, Wiseman J, Ward P, and Williamson RA (2009b) In vitro characterization of GSK256066, an exceptionally high affinity and selective inhibitor of PDE4 suitable for administration by inhalation. Am J Rev Crit Care Med 179:A4581.
23. Kuss H, Hoefgen N, Johanssen S, Kronbach T, and Rundfeldt C (2003) In vivo efficacy in airway disease models of N-(3,5-dichloro-pyrid-4-yl)-{1-(4- fluorobenzyl)- 5-hyroxy-indole-3-yl}-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration. J Pharmacol Exp Ther 307:373-385.
24. Pauwels RA, Kips JC, Peleman RA, and Van Der StraetenME(1990) The effect of endotoxin inhalation on airway responsiveness and cellular influx in rats. Am Rev Respir Dis 141:540-545. (Pubitemid 20109134)
25. Press NJ and Banner KH (2009) PDE4 inhibitors- a review of the current field. Prog Med Chem 47:37-74.
26. Singh D, Petavy F, MacDonald AJ, Lazaar AL, and O'Connor BJ (2010) The unhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Respir Res 11:26.
27. Spina D (2008) PDE4 inhibitors: current status. Br J Pharmacol 155:308-315.
28. Torphy TJ (1998) Phosphodiesterase enzymes: molecular targets for novel antiasthma drugs. Am J Resp Crit Care Med 157:351-370.
29. Tralau-Stewart CJ, Williamson RA, Nials AT, Gascoigne MH, Dawson J, Hart GJ, Angell ADR, Solanke YE, Lucas FL, Wiseman J, et al. (2010) GSK256066, an exceptionally high-affinity and selective inhibitor of PDE4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther doi:10.1124/jpet.110.173690.
30. Trevethick M, Banner K, Ballard S, Barnard A, Lewis A, Browne J, Sims G, Mansfield F, Brown C, Salmon G, et al. (2007) UK-500,001 a potent selective inhibitor of phosphodiesterase type 4 (PDE4) designed for inhaled delivery, inhibits TNF alpha, MIP1beta and LTB4 release from native human blood cells. Am J Respir Crit Care 175:A927.
31. Underwood DC, Bochnowicz S, Osborn RR, Kotzer CJ, Luttmann MA, Hay DW, Gorycki PD, Christensen SB, and Torphy TJ (1998) Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB207499 (Ariflo) in the guinea pig. J Pharmacol Exp Ther 287:988-995. (Pubitemid 29131612)
32. Vestbo J, Tan L, Atkinson G, Ward J, and the UK-500-001 Global Study Team (2009) A controlled trial of 6 weeks' treatment with a novel, inhaled phosphodiesterase type 4 inhibitor in COPD. Eur Respir J 33: 1039-1044.
33. Woodrow MD, Ballantine SP, Barker MD, Clarke BJ, Dawson J, Dean TW, Delves CJ, Evans B, Gough SL, Guntrip SB, et al. (2009) Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration. Bioorg Med Chem Lett 19:5261-5265.