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GSK256066

现货
Catalog No.
A4331
PDE4的高效选择性抑制剂
组合的产品项目
规格价格库存 数量
10mg
¥ 2,590.00
现货
50mg
¥ 7,490.00
Ship with 10-15 days
200mg
¥ 17,290.00
Ship with 10-15 days

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Background

Apparent IC50 3.2 pM, steady state IC50 < 0.5 pM

GSK256066 is an exceptionally high-affinity and selective inhibitor of PDE4 designed for inhaled delivery.

Oral phosphodiesterase (PDE) 4 inhibitors have demonstrated clinical efficacy in chronic obstructive pulmonary disease and asthma.

In vitro: GSK256066 is a slow- and tight-binding inhibitor of PDE4B, more potent than any previously documented compound, for example roflumilast, tofimilast and cilomilast [1].

In vivo: When administered by the intratracheal route to rats, GSK256066 inhibited LPS-induced pulmonary neutrophilia with ED50s 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) [1].

Clinical trial: Administration of inhaled GSK256066 was well-tolerated in patients with moderate COPD. Further studies would be required to confirm the favorable safety profile and to demonstrate clinical efficacy of this compound [2].

References:
[1] Tralau-Stewart CJ, Williamson RA, Nials AT, Gascoigne M, Dawson J, Hart GJ, Angell AD, Solanke YE, Lucas FS, Wiseman J, Ward P, Ranshaw LE, Knowles RG.  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):145-54.
[2] Watz H, Mistry SJ, Lazaar AL; IPC101939 investigators.  Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD. Pulm Pharmacol Ther. 2013;26(5):588-95.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt518.58
Cas No.801312-28-7
FormulaC27H26N4O5S
Solubility<1.04 mg/mL in DMSO, <2.09 mg/mL in EtOH, <2.29 mg/mL in H2O
Chemical Name6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide
SDFDownload SDF
Canonical SMILESCC1=C2C(=CC(=C1)S(=O)(=O)C3=CC=CC(=C3)C(=O)N(C)C)C(=C(C=N2)C(=O)N)NC4=CC(=CC=C4)OC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

人外周血单核细胞(PBMCs)

溶解方法

在DMSO中的溶解度有限。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0.1 pM-1 nM,20 h

应用

在LPS刺激的PBMCs和全血中,GSK256066有效地抑制肿瘤坏死因子ɑ(TNFɑ)的产生,IC50分别为0.01 nM和126 pM。在PBMCs和全血中,GSK256066均比其他测试的化合物更强效。

临床实验[2]:

临床样本

40-75岁的慢性阻塞性肺病(COPD)病人

剂量

25 mg或87.5 mg,每天一次,持续28天

应用

GSK256066是强效的吸入性PDE 4抑制剂,在中度慢性阻塞性肺病病人中具有很好的耐受性,不会增加胃肠道的不良反应。给药87.5 mg GSK256066的病人肺功能有改善的趋势,有可能减少肺过度充气。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[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 characterization[J]. Journal of Pharmacology and Experimental Therapeutics, 2011, 337(1): 145-154.

[2]. Watz H, Mistry S J, Lazaar A L. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD[J]. Pulmonary pharmacology & therapeutics, 2013, 26(5): 588-595.

生物活性

Description GSK256066是磷酸二酯酶4(PDE4)的高效选择性抑制剂,IC50值为3.2 pM。
靶点 PDE4          
IC50 3.2 pM          

质量控制