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Phosphodiesterase 4 (PDE 4) enzymes are the principal phosphodiesterases responsible for the hydrolysis of cAMP in pro-inflammatory leukocytes. The functional consequences of elevating cAMP in these cells suggests that inhibition of PDE 4 offers a novel approach to asthma therapy. However, clinical development of early inhibitors has been limited by the side-effect of nausea. In this review, we detail how the molecular biology of the PDE 4 gene family has been integrated with biochemical, cellular and pharmacological studies. This approach has led to the discovery and development of CDP840, a prototype inhibitor for which efficacy has been demonstrated in a clinical model of asthma in the absence of side-effects.

Original publication

DOI

10.1016/S1359-6446(97)01000-3

Type

Journal article

Journal

Drug Discovery Today

Publication Date

01/03/1997

Volume

2

Pages

89 - 101