GSK256066 is a selective PDE4B (equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, showing > 380,000-fold selectivity versus PDE1/2/3/5/6 and > 2500-fold selectivity against PDE4B versus PDE7.
Phosphodiesterases (PDEs) are a class of enzymes that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which are composed of 11 different families and each family contains different subtypes[3]. GSK256066 is a selective PDE4B inhibitor with IC50 of 3.2 pM. Consistent with its potency, GSK256066 inhibited tumor necrosis factor α production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes with 0.01 nM IC50 and by LPS-stimulated whole blood with 126 pM IC50[4]. When administered intratracheally to rats, GSK256066 inhibited LPS-induced pulmonary neutrophilia with ED50 values of 1.1 μg/kg (aqueous suspension) and 2.9 μg/kg (dry powder formulation) and was more potent than an aqueous suspension of the corticosteroid fluticasone propionate (ED50 9.3 μg/kg)[4].
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