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Chemical Compound Review

Ariflo     4-cyano-4-(3-cyclopentyloxy- 4-methoxy...

Synonyms: Cilomilast, SureCN26372, SureCN27515, SureCN27516, Ariflo (TN), ...
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Disease relevance of Cilomilast


High impact information on Cilomilast


Chemical compound and disease context of Cilomilast


Biological context of Cilomilast


Anatomical context of Cilomilast


Associations of Cilomilast with other chemical compounds


Gene context of Cilomilast


Analytical, diagnostic and therapeutic context of Cilomilast

  • Cilomilast (Ariflo, SB 207499, SmithKline Beecham), the most advanced member of the class in Phase III clinical trials, was reported to have a limited therapeutic window [26].
  • In this model, topical administration of SB 207499 (1000 microgram) inhibited intralesional concentrations of interleukin-4 (55%; P <.01) [5].
  • Effects of cilomilast, a selective phosphodiesterase 4 inhibitor, on esophageal motility and pH, and orocecal and colonic transit: two single-center, randomized, double-blind, placebo-controlled, two-part crossover studies in healthy volunteers [27].
  • The point estimate (90% CI) for the difference in day 24 INR values between cilomilast and placebo (adjusted for baseline) was 0.02 (90% CI-0.13 to 0.17), which translates to an INR ratio of 1.02 (90% CI 0.91 to 0.13) [12].
  • STUDY SELECTION AND DATA EXTRACTION: All clinical trials evaluating cilomilast and published in English were included in this review [28].


  1. Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study. Compton, C.H., Gubb, J., Nieman, R., Edelson, J., Amit, O., Bakst, A., Ayres, J.G., Creemers, J.P., Schultze-Werninghaus, G., Brambilla, C., Barnes, N.C. Lancet (2001) [Pubmed]
  2. PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease. Banner, K.H., Trevethick, M.A. Trends Pharmacol. Sci. (2004) [Pubmed]
  3. Phosphodiesterase 4 inhibitor cilomilast inhibits fibroblast-mediated collagen gel degradation induced by tumor necrosis factor-alpha and neutrophil elastase. Kohyama, T., Liu, X., Zhu, Y.K., Wen, F.Q., Wang, H.J., Fang, Q., Kobayashi, T., Rennard, S.I. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  4. Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB 207499 (Ariflo) in the guinea pig. Underwood, D.C., Bochnowicz, S., Osborn, R.R., Kotzer, C.J., Luttmann, M.A., Hay, D.W., Gorycki, P.D., Christensen, S.B., Torphy, T.J. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  5. SB 207499 (Ariflo), a second generation phosphodiesterase 4 inhibitor, reduces tumor necrosis factor alpha and interleukin-4 production in vivo. Griswold, D.E., Webb, E.F., Badger, A.M., Gorycki, P.D., Levandoski, P.A., Barnette, M.A., Grous, M., Christensen, S., Torphy, T.J. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  6. Chronic obstructive pulmonary disease: emerging therapies. Hay, D.W. Current opinion in chemical biology. (2000) [Pubmed]
  7. Phosphodiesterase 4 Inhibitors for the Treatment of Asthma and COPD. Huang, Z., Mancini, J.A. Current medicinal chemistry (2006) [Pubmed]
  8. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. Gamble, E., Grootendorst, D.C., Brightling, C.E., Troy, S., Qiu, Y., Zhu, J., Parker, D., Matin, D., Majumdar, S., Vignola, A.M., Kroegel, C., Morell, F., Hansel, T.T., Rennard, S.I., Compton, C., Amit, O., Tat, T., Edelson, J., Pavord, I.D., Rabe, K.F., Barnes, N.C., Jeffery, P.K. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  9. Clinical pharmacology of Cilomilast. Down, G., Siederer, S., Lim, S., Daley-Yates, P. Clinical pharmacokinetics. (2006) [Pubmed]
  10. Comparison of PDE 4 inhibitors, rolipram and SB 207499 (ariflo), in a rat model of pulmonary neutrophilia. Spond, J., Chapman, R., Fine, J., Jones, H., Kreutner, W., Kung, T.T., Minnicozzi, M. Pulmonary pharmacology & therapeutics. (2001) [Pubmed]
  11. Cilomilast (Ariflo) does not potentiate the cardiovascular effects of inhaled salbutamol. Murdoch, R.D., Cowley, H., Kelly, J., Higgins, R., Webber, D. Pulmonary pharmacology & therapeutics. (2002) [Pubmed]
  12. Warfarin pharmacodynamics unaffected by cilomilast. Kelly, J., Murdoch, R.D., Clark, D.J., Webber, D.M., Fuder, H. The Annals of pharmacotherapy. (2001) [Pubmed]
  13. Effect of cilomilast (Ariflo) on TNF-alpha, IL-8, and GM-CSF release by airway cells of patients with COPD. Profita, M., Chiappara, G., Mirabella, F., Di Giorgi, R., Chimenti, L., Costanzo, G., Riccobono, L., Bellia, V., Bousquet, J., Vignola, A.M. Thorax (2003) [Pubmed]
  14. Effect of PDE4 inhibitors on zymosan-induced IL-8 release from human neutrophils: synergism with prostanoids and salbutamol. Au, B.T., Teixeira, M.M., Collins, P.D., Williams, T.J. Br. J. Pharmacol. (1998) [Pubmed]
  15. A comparison of the inhibitory activity of PDE4 inhibitors on leukocyte PDE4 activity in vitro and eosinophil trafficking in vivo. Cooper, N., Teixeira, M.M., Warneck, J., Miotla, J.M., Wills, R.E., Macari, D.M., Gristwood, R.W., Hellewell, P.G. Br. J. Pharmacol. (1999) [Pubmed]
  16. PDE4 inhibitors attenuate fibroblast chemotaxis and contraction of native collagen gels. Kohyama, T., Liu, X., Wen, F.Q., Zhu, Y.K., Wang, H., Kim, H.J., Takizawa, H., Cieslinski, L.B., Barnette, M.S., Rennard, S.I. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  17. Cilomilast: pharmacokinetic and pharmacodynamic interactions with digoxin. Zussman, B.D., Kelly, J., Murdoch, R.D., Clark, D.J., Mbchb, n.u.l.l., Schubert, C., Collie, H. Clinical therapeutics. (2001) [Pubmed]
  18. TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines. Bäumer, W., Seegers, U., Braun, M., Tschernig, T., Kietzmann, M. Br. J. Dermatol. (2004) [Pubmed]
  19. Lack of pharmacokinetic interactions between cilomilast and theophylline or smoking in healthy volunteers. Murdoch, R.D., Zussman, B., Schofield, J.P., Webber, D.M. Journal of clinical pharmacology. (2004) [Pubmed]
  20. Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice. Leclerc, O., Lagente, V., Planquois, J.M., Berthelier, C., Artola, M., Eichholtz, T., Bertrand, C.P., Schmidlin, F. Eur. Respir. J. (2006) [Pubmed]
  21. Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth-muscle cells. Modulation by cyclic adenosine monophosphate. Ammit, A.J., Hoffman, R.K., Amrani, Y., Lazaar, A.L., Hay, D.W., Torphy, T.J., Penn, R.B., Panettieri, R.A. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  22. Phosphodiesterase 4 inhibition of {beta}2-integrin adhesion caused by leukotriene B4 and TNF-{alpha} in human neutrophils. Meliton, A.Y., Mu??oz, N.M., Lambertino, A., Boetticher, E., Learoyd, J., Zhu, X., Leff, A.R. Eur. Respir. J. (2006) [Pubmed]
  23. Cyclic AMP-specific phosphodiesterase 4 inhibitors promote ABCA1 expression and cholesterol efflux. Lin, G., Bornfeldt, K.E. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  24. The novel phosphodiesterase 4 inhibitor, CI-1044, inhibits LPS-induced TNF-alpha production in whole blood from COPD patients. Ouagued, M., Martin-Chouly, C.A., Brinchault, G., Leportier-Comoy, C., Depincé, A., Bertrand, C., Lagente, V., Belleguic, C., Pruniaux, M.P. Pulmonary pharmacology & therapeutics. (2005) [Pubmed]
  25. Structural basis for the activity of drugs that inhibit phosphodiesterases. Card, G.L., England, B.P., Suzuki, Y., Fong, D., Powell, B., Lee, B., Luu, C., Tabrizizad, M., Gillette, S., Ibrahim, P.N., Artis, D.R., Bollag, G., Milburn, M.V., Kim, S.H., Schlessinger, J., Zhang, K.Y. Structure (Camb.) (2004) [Pubmed]
  26. The next generation of PDE4 inhibitors. Huang, Z., Ducharme, Y., Macdonald, D., Robichaud, A. Current opinion in chemical biology. (2001) [Pubmed]
  27. Effects of cilomilast, a selective phosphodiesterase 4 inhibitor, on esophageal motility and pH, and orocecal and colonic transit: two single-center, randomized, double-blind, placebo-controlled, two-part crossover studies in healthy volunteers. Houghton, L.A., Atkinson, W., Whorwell, P.J., Morris, J., Murdoch, R.D., Cooper, S.M., Webber, D.M., Walls, C.M. Clinical therapeutics. (2006) [Pubmed]
  28. Cilomilast: orally active selective phosphodiesterase-4 inhibitor for treatment of chronic obstructive pulmonary disease. Martina, S.D., Ismail, M.S., Vesta, K.S. The Annals of pharmacotherapy. (2006) [Pubmed]
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