GSK256066

801312-28-7

C27H26N4O5S

DMSO : < 1 mg/mL (insoluble or slightly soluble)

Metabolic Enzyme/Protease

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380, 000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. IC50 value: 3.2 pM [1] Target: PDE4B in vitro: GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFalpha production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 x 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 x 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity [1]. in vivo: GSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 ug/kg, achieving maximal inhibition of 72% at 30 ug/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 ug/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 ml/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the male CD rat [1]. GSK256066 sustains at a high lung concentration of 2.6 ug/g after intra-tracheal administration as an aqueous suspension at a dose of 30 ug/kg in rats [2]. GSK256066 (10 ug/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3�100 ug/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 ug/kg in rat. GSK256066 (10 ug/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 ug/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 ug/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 ug/kg without inducing emetic episodes [3].