GSK256066 is a potent phosphodiesterase 4 (PDE4) inhibitor (IC50s = 4.9, 3.2, 3.8, and 1.1 pM for PDE4A, PDE4B, PDE4C, and PDE4D, respectively).1 It is greater than 380,000-fold selective for PDE4 over PDE1-3, -5, and -6 and greater than 2,500-fold selective over PDE7. GSK256066 inhibits LPS-induced TNF-α production in human peripheral blood monocytes (IC50 = 0.01 nM) and human whole blood (IC50 = 126 pM). Intratracheal administration of GSK256066 inhibits LPS-induced pulmonary neutrophilia in rats (ED50 = 1.1 ?g/kg). It inhibits ovalbumin-induced pulmonary eosinophilia in rats (ED50 = 0.4 ?g/kg) and LPS-induced pulmonary neutrophilia in ferrets (ED50 = 18 ?g/kg).2
1.Tralau-Stewart, C.J., Williamson, R.A., Nials, A.T., et al.GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: In vitro, kinetic, and in vivo characterizationJ. Pharmacol. Exp. Ther.337(1)145-154(2011) 2.Nials, A.T., Tralau-Stewart, C.J., Gascoigne, M.H., et al.In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitorJ. Pharmacol. Exp. Ther.337(1)137-144(2011)