GSK356278 is a potent, selective, and orally bioavailable phosphodiesterase 4 (PDE4) inhibitor with anxiolytic and cognition-improving effects.1 It is greater than 100-fold selective for PDE4A, -B, and -D (IC50s = 2.51, 1.58, and 2 nM for PDE4A, PDE4B, and PDE4D, respectively) over 10 other members of the PDE family, as well as over a panel of 154 diverse receptors, ion channels, and enzymes. It inhibits LPS-induced release of TNF-α in isolated human whole blood (IC50 = 23.1 nM) and reduces LPS-induced neutrophilia in rats (ED50 = 0.09 mg/kg). GSK356278 (0.01-1 mg/kg) induces anxiolytic behavior in marmosets, and improves performance of non-human primates in an object retrieval test when administered at a dose of 1 mg/kg.
1.Rutter, A.R., Poffe, A., Cavallini, P., et al.GSK356278, a potent, selective, brain-penetrant phosphodiesterase 4 inhibitor that demonstrates anxiolytic and cognition-enhancing effects without inducing side effects in preclinical speciesJ. Pharmacol. Exp. Ther.350(1)153-163(2014)