The in vitro pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long acting β2-adrenoceptor agonist

Journal of Pharmacology and Experimental Therapeutics

Volumn 349, Issue 4, 2014, Pages 85-93

  Tannheimer, Stacey L ^a   Sorensen, Eric A ^a   Cui, Zhi Hua ^a   Kim, Musong ^b   Patel, Leena ^b   Baker, William R ^b   Phillips, Gary B ^b   Wright, Clifford D ^a   Salmon, Michael ^a,c  

^a Gilead Sciences   (United States)

^b GILEAD SCIENCES INC   (United States)

^c MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENERGIC BETA-2 RECEPTOR AGONISTS; ANIMALS; CELL CULTURE TECHNIQUES; CYTOKINES; FIBROBLASTS; GUINEA PIGS; HUMANS; LEUKOCYTES, MONONUCLEAR; LIPOPOLYSACCHARIDES; MALE; MOLECULAR STRUCTURE; MUSCLE, SMOOTH; PHOSPHODIESTERASE 4 INHIBITORS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; QUINOLONES; RESPIRATORY SYSTEM; SULFONES; TIME FACTORS;

EID: 84896474573     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.113.210997     Document Type: Article

References (34)

1. Baker WR, Cai S, Kaplan JA, Kim M, Loyer-Drew JA, Perrault S, Phillips G, Purvis LJ, Stasiak M, Stevens KL, and Van Veldhuizen J (2011), inventors; Gilead Sciences, Inc., assignee. Bifunctional quinoline derivatives. World Patent WO/2011/143105. 2011 Sept 5.
2. Bender AT and Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488-520.
3. Bilski AJ, Halliday SE, Fitzgerald JD, and Wale JL (1983) The pharmacology of a beta 2-selective adrenoceptor antagonist (ICI 118,551). J Cardiovasc Pharmacol 5:430-437.
4. Bissonnette EY and Befus AD (1997) Anti-inflammatory effect of beta 2-agonists: inhibition of TNF-alpha release from human mast cells. J Allergy Clin Immunol 100:825-831.
5. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, and Vestbo J; TORCH Investigators (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356:775-789.
6. Cazzola M (2010) The divergent opinions of regulatory authorities on roflumilast are puzzling but we need new drugs for treating chronic obstructive pulmonary disease. Ther Adv Respir Dis 4:195-198.
7. Chapman RW, House A, Richard J, Prelusky D, Lamca J, Wang P, Lundell D, Wu P, Ting PC, and Lee JF, et al. (2010) Pharmacology of a potent and selective inhibitor of PDE4 for inhaled administration. Eur J Pharmacol 643:274-281.
8. Chong LK, Cooper E, Vardey CJ, and Peachell PT (1998) Salmeterol inhibition of mediator release from human lung mast cells by beta-adrenoceptor-dependent and independent mechanisms. Br J Pharmacol 123:1009-1015.
9. Donnelly LE, Tudhope SJ, Fenwick PS, and Barnes PJ (2010) Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages. Eur Respir J 36:178-186.
10. Donohue JF (2004) Therapeutic responses in asthma and COPD. Bronchodilators. Chest 126(2, Suppl)125S-137S, discussion 159S-161S.
11. Gross NJ, Giembycz MA, and Rennard SI (2010) Treatment of chronic obstructive pulmonary disease with roflumilast, a new phosphodiesterase 4 inhibitor. COPD 7: 141-153.
12. Hatzelmann A, Morcillo EJ, Lungarella G, Adnot S, Sanjar S, Beume R, Schudt C, and Tenor H (2010) The preclinical pharmacology of roflumilast - a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther 23:235-256.
13. Houslay MD (2010) Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem Sci 35:91-100.
14. Johannessen M, Delghandi MP, and Moens U (2004) What turns CREB on? Cell Signal 16:1211-1227.
15. Jones PW, Barnes N, Vogelmeier C, Lawrence D, and Kramer B (2011) Efficacy of indacaterol in the treatment of patients with COPD. Prim Care Respir J 20: 380-388.
16. 2-adrenoceptor agonist, augments GRE-dependent transcription in human airway epithelial cells. Am J Respir Crit Care Med 185:A5693.
17. Kaur M, Beardsall M, Salmon M, and Singh D (2012) GS-5759, a novel bi-functional phosphodiesterase 4 inhibitor and long-acting β2-adrenoceptor agonist inhibits cytokine production from COPD alveolar macrophages. Am J Respir Crit Care Med 185:A5705.
18. Lemoine H, Ehle B, and Kaumann AJ (1985) Direct labelling of beta 2-adrenoceptors. Comparison of binding potency of 3H-ICI 118,551 and blocking potency of ICI 118,551. Naunyn Schmiedebergs Arch Pharmacol 331:40-51.
19. Matera MG, Page CP, and Cazzola M (2011) Novel bronchodilators for the treatment of chronic obstructive pulmonary disease. Trends Pharmacol Sci 32:495-506.
20. Moodley T, Wilson SM, Joshi T, Rider CF, Sharma P, Yan D, Newton R, and Giembycz MA (2013) Phosphodiesterase 4 inhibitors augment the ability of formoterol to enhance glucocorticoid-dependent gene transcription in human airway epithelial cells: a novel mechanism for the clinical efficacy of roflumilast in severe chronic obstructive pulmonary disease. Mol Pharmacol 83:894-906.
21. Nials AT, Tralau-Stewart CJ, Gascoigne MH, Ball DI, Ranshaw LE, and Knowles RG (2011) In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitor. J Pharmacol Exp Ther 337:137-144.
22. Phillips G and Salmon M (2012) Bifunctional compounds for the treatment of COPD, in Annual Report in Medicinal Chemistry (Desai MC ed) volume 47, pp. 209-221, Elsevier Inc., New York.
23. Robinson C, Zhang J, Garrod DR, Newton GK, Jenkins K, and Perrior TR (2011) Future inhaled drugs by virtual innovation: allergen delivery inhibitors. Future Med Chem 3:1567-1570.
24. Sabatini F, Petecchia L, Boero S, Silvestri M, Klar J, Tenor H, Beume R, Hatzelmann A, and Rossi GA (2010) A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro. Pulm Pharmacol Ther 23:283-291.
25. Saldou N, Obernolte R, Huber A, Baecker PA, Wilhelm R, Alvarez R, Li B, Xia L, Callan O, and Su C, et al. (1998) Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell Signal 10:427-440.
26. Seldon PM, Meja KK, and Giembycz MA (2005) Rolipram, salbutamol and prostaglandin E2 suppress TNFalpha release from human monocytes by activating Type II cAMP-dependent protein kinase. Pulm Pharmacol Ther 18:277-284.
27. Spina D (2008) PDE4 inhibitors: current status. Br J Pharmacol 155:308-315.
28. Tannheimer SL, Sorensen EA, Haran AC, Mansfield CN, Wright CD, and Salmon M (2012a) Additive anti-inflammatory effects of beta 2 adrenoceptor agonists or glucocorticosteroid with roflumilast in human peripheral blood mononuclear cells. Pulm Pharmacol Ther 25:178-184.
29. Tannheimer SL, Wright CD, and Salmon M (2012b) Combination of roflumilast with a beta-2 adrenergic receptor agonist inhibits proinflammatory and profibrotic mediator release from human lung fibroblasts. Respir Res 13:28.
30. Tashkin DP and Fabbri LM (2010) Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents. Respir Res 11: 149-163.
31. Togo S, Liu X, Wang X, Sugiura H, Kamio K, Kawasaki S, Kobayashi T, Ertl RF, Ahn Y, and Holz O, et al. (2009) PDE4 inhibitors roflumilast and rolipram augment PGE2 inhibition of TGF-beta1-stimulated fibroblasts. Am J Physiol Lung Cell Mol Physiol 296:L959-L969.
32. Tralau-Stewart CJ, Williamson RA, Nials AT, Gascoigne M, Dawson J, Hart GJ, Angell AD, Solanke YE, Lucas FS, and Wiseman J, et al. (2011) GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther 337:145-154.
33. Undem BJ, Peachell PT, and Lichtenstein LM (1988) Isoproterenol-induced inhibition of immunoglobulin E-mediated release of histamine and arachidonic acid metabolites from the human lung mast cell. J Pharmacol Exp Ther 247:209-217.
34. 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 SB 207499 (Ariflo) in the guinea pig. J Pharmacol Exp Ther 287:988-995.