Topical anti-inflammatory activity of DuP 654, a 2-substituted 1-naphthol

Recent work suggests that one of the common biochemical characteristics of skin inflammatory diseases such as psoriasis is altered arachidonic acid metabolism with elevated levels of prostaglandins and leukotrienes. DuP 654, a 2-substituted 1-naphthol, is an exceptionally potent inhibitor of 5-lipoxygenase. DuP 654 was tested in various models of skin inflammation and was found to be potent at inhibiting edema induced by the topical application of arachidonic acid, tetradecanoyl phorbol acetate or the calcium ionophore A23187. DuP 654 was also effective in a murine model of contact sensitivity. DuP 654 was effective at reducing the numbers of infiltrating polymorphonuclear leukocytes in AA and TPA induced edema. These data, taken together, suggest that DuP 654 may be effective in treating human skin diseases.