Biology Reference
In-Depth Information
selective PDE4 inhibitors, use of mixed PDE inhibitors, interference with PDE4
activation, targeting proteins that are involved in locating PDE4 to specific micro-
cellular domains and finally the potential for use of antisense oligonucleotides may
offer another solution to the problem of targeting PDE4 in inflammation is a cause
for optimism.
Conflict of Interest.
The authors are consultants for Veronapharma plc who are
developing RPL554 as a novel inhaled PDE3/4 inhibitor for the treatment of inflam-
matory airways disease. CP is also a founder and has equity in Veronapharma plc.
References
Abraham C, Cho JH (2009) Inflammatory bowel disease. N Engl J Med 361:2066-2078
Akama T, Baker SJ, Zhang YK, Hernandez V, Zhou H, Sanders V, Freund Y, Kimura R,
Maples KR, Plattner JJ (2009) Discovery and structure-activity study of a novel benzoxaborole
anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic
dermatitis. Bioorg Med Chem Lett 19:2129-2132
Aoki M, Kobayashi M, Ishikawa J, Saita Y, Terai Y, Takayama K, Miyata K, Yamada T (2000)
A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1, 7-diethylpyrido
[2, 3-d]pyrimidin-2(1H)-one), with little emetogenic activity. J Pharmacol Exp Ther 295:
255-260
Aoki M, Fukunaga M, Sugimoto T, Hirano Y, Kobayashi M, Honda K, Yamada T (2001) Studies
on mechanisms of low emetogenicity of YM976, a novel phosphodiesterase type 4 inhibitor.
J Pharmacol Exp Ther 298:1142-1149
Ariga M, Neitzert B, Nakae S, Mottin G, Bertrand C, Pruniaux MP, Jin SL, Conti M (2004)
Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site
of inflammation. J Immunol 173:7531-7538
Banner KH, Press NJ (2009) Dual PDE3/4 inhibitors as therapeutic agents for chronic obstructive
pulmonary disease. Br J Pharmacol 157:892-906
Barber R, Baillie GS, Bergmann R, Shepherd MC, Sepper R, Houslay MD, Heeke GV (2004)
Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of
smokers with COPD, smokers without COPD, and nonsmokers. Am J Physiol Lung Cell Mol
Physiol 287:L332-L343
Barnes PJ (2008) The cytokine network in asthma and chronic obstructive pulmonary disease.
J Clin Invest 118:3546-3556
Barnes PJ, Adcock IM, Ito K (2005) Histone acetylation and deacetylation: importance in
inflammatory lung diseases. Eur Respir J 25:552-563
Baumer W, Hoppmann J, Rundfeldt C, Kietzmann M (2007) Highly selective phosphodiesterase
4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug
Targets 6:17-26
Boolell M, Gepi-Attee S, Gingell JC, Allen MJ (1996) Sildenafil, a novel effective oral therapy for
male erectile dysfunction. Br J Urol 78:257-261
Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP (2006a) The pharmacology
of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9, 10-dimethoxy-2(2, 4,
6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl) -3, 4, 6, 7-tetrahydro-2H-pyrimido[6, 1-a]
isoquinolin-4-one] and RPL565 [6, 7-dihydro-2-(2, 6-diisopropylphenoxy)-9, 10-dimethoxy-
4H-pyrimido[6, 1-a]i soquinolin-4-one]. J Pharmacol Exp Ther 318:840-848
Boswell-Smith V, Spina D, Page CP (2006b) Phosphodiesterase inhibitors. Br J Pharmacol 147
(Suppl 1):S252-S257
