Phosphodiesterase 7 (PDE7) as a therapeutic target

The concept that targeting phosphodiesterase type 4 (PDE4) with small-molecule inhibitors could lead to the discovery of novel, steroid-sparing compounds with utility in treating a multitude of diseases associated with chronic inflammation has gained general acceptance over the last 20 years. A fundamental obstacle that has yet to be overcome is to develop compounds that dissociate beneficial from adverse events. Unfortunately, both of these activities of PDE4 inhibitors represent an extension of their pharmacology and improving the therapeutic ratio has proved to be a major challenge. Several strategies have been considered with some degree of success, but compounds with an optimal pharmacophore that have been validated in human subjects have not yet been reported. An alternative approach is to inhibit other cAMP PDE families that are also expressed in immune and proinflammatory cells, in the hope that the beneficial activity can be retained in the absence of side effects. One such candidate is PDE7. In this article we review the literature on PDE7 and explore the possibility that selective small-molecule inhibitors of this enzyme family could provide a novel approach to treat a variety of immunological and immunodeficiency conditions.