生物活性

• 描述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].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00549744	Asthma	Phase 2	Completed	-	New Zealand ... more >> GSK Investigational Site Wellington, New Zealand, 6035 South Africa GSK Investigational Site George, Eastern Cape, South Africa, 6529 GSK Investigational Site Bloemfontein, South Africa, 9301 Collapse <<
  NCT00377728	Rhinitis, Allergic, Seasonal ... more >> Seasonal Allergic Rhinitis Collapse <<	Phase 2	Completed	-	Austria ... more >> GSK Investigational Site Vienna, Austria, A-1150 Collapse <<
  NCT00549679	Pulmonary Disease, Chronic Obs... more >>tructive Collapse <<	Phase 2	Completed	-	Estonia ... more >> GSK Investigational Site Tallinn, Estonia, 13419 Finland GSK Investigational Site Tampere, Finland, 33520 Germany GSK Investigational Site Gauting, Bayern, Germany, 82131 GSK Investigational Site Berlin, Germany, 10717 GSK Investigational Site Hamburg, Germany, 22291 Netherlands GSK Investigational Site Hoorn, Netherlands, 1624 NP GSK Investigational Site Horn, Netherlands, 6085 NM GSK Investigational Site Veldhoven, Netherlands, 5504 DB Russian Federation GSK Investigational Site Barnaul, Russian Federation, 656 045 GSK Investigational Site Moscow, Russian Federation, 105 077 GSK Investigational Site St. Petersburg, Russian Federation, 197022 GSK Investigational Site Yaroslavl, Russian Federation, 150003 Slovakia GSK Investigational Site Bratislava, Slovakia, 826 06 GSK Investigational Site Kosice, Slovakia, 041 90 GSK Investigational Site Martin, Slovakia, 036 59 Collapse <<

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• 参考文献

• [1] Tralau-Stewart CJ, Williamson RA, et al. GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54.

  [2] Woodrow MD, Ballantine SP, et al. Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5261-5.

  [3] Peng T, Gong J, Jin Y, et al. Inhibitors of phosphodiesterase as cancer therapeutics. Eur J Med Chem. 2018;150:742–756.

  [4] Tralau-Stewart CJ, Williamson RA, Nials AT, et al. GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther. 2011;337(1):145–154.