GSK256066CAS号: 801312-28-7分子式: C27H26N4O5S分子量: 518.58描述纯度储存/保存方法可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)参考文献
产品描述 | |
描述 |
GSK256066是一种选择性的PDE4B(与A-D亚型具有相等的亲和力)抑制剂,IC50为3.2 pM,比作用于PDE1/2/3/5/6选择性高380,000倍以上,作用于PDE4B比作用于PDE7选择性高2500倍以上。GSK256066 是缓慢但紧密结合的PDE4B抑制剂,IC50为3.2 pM。GSK256066作用于PBMCs,强有效抑制LPS刺激的TNFα产生,pIC50 为11.0,IC50 为10 pM,GSK256066作用于人全血培养物,pIC50为9.90,IC50为 126 pM。GSK256066高选择性抑制 PDE4(是抑制PDE1,PDE2, PDE3, PDE5, 和PDE6的3.8×105多倍,是抑制PDE7的2.5×103多倍)。 |
纯度 |
98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
可溶性/溶解性 |
DMSO :5 mg/mL (9.64 mM)
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生物活性 | |
靶点 |
PDE4B
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In vitro(体外研究) |
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 TNFα 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 × 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity.
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In vivo(体内研究) |
GSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/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. GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats. GSK256066 (10 μg/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 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes.
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参考文献 | |
参考文献 |
In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitor.
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分子结构图