Cilomilast

A potent and selective PDE4 inhibitor with IC50 of 95/120 nM for LPDE4/HPDE4; shows selectivity for PDE4 over the other PDE isozymes and is 75-fold more selective than (R) -rolipram with respect to LPDE4 activity versus HPDE4 activity; inhibits antigen-induced bronchoconstriction in conscious guinea pigs at 30 mg/kg and orally acitive.COPD Phase 3 Discontinued (In Vitro) :Cilomilast (0.1 nM-10 μM; 5 min) inhibits human neutrophil functions.Cilomilast (0.1 nM-10 μM; 5 min) inhibits eosinophil chemiluminescence response.Cilomilast (0.001-100 μM; 30 min) inhibits the synthesis of TNFα in human monocytes and in human whole blood. (In Vivo) :SB-207499 (1-100 mg/kg; p.o.) significantly inhibits the production of human TNFα in a dose-dependent manner in mice.SB-207499 (0.1-100 mg/kg; oral gavage) reverses reserpine-induced hypothermia in mice, with an ED50 of 2.3 mg/kg.SB-207499 (500 μg/ear; b.i.d. for 6 d) inhibits the chronic oxazolone-induced inflammatory response and intralesional IL-4 concentrations in mice.