YM976 is a potent, selective phosphodiesterase type 4 (PDE4) inhibitor with IC50 of 2.2 nM against PDE4 purified from human peripheral leukocytes. YM976 has no effects on the other PDE isozymes, PDE1, -2, -3, and -5. YM976 potentiates prostaglandin E(2)-induced cAMP accumulation in a human mononuclear cell line, U937, and YM976 inhibits TNF-alpha production from human peripheral blood mononuclear cells stimulated by lipopolysaccharide. YM976 inhibits the cell infiltration into the pleural cavity with oral ED(30) values of 9.1 mg/kg in rat carrageenan-induced pleurisy models. YM976 dose dependently reduces carrageenan-induced leukocyte infiltration at the doses of 1, 3, and 10 mg/kg, p.o.
