GSK256066
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
表观IC50为3.2 pM,稳态IC50 小于0.5 pM。
GSK256066是PDE4的高亲和力选择性抑制剂,可吸入性治疗。
在慢性阻塞性肺疾病和哮喘患者中,口服磷酸二酯酶(PDE)4抑制剂具有临床有效性。
体外实验:GSK256066是PDE4B的缓慢的紧密结合的抑制剂,相比之前得到的化合物更为有效,例如罗氟司特(roflumilast)、罗氟司特(tofimilast)和西洛司特(cilomilast )[1]。
在体实验:当通过气管途径给予大鼠GSK256066,抑制LPS诱导的肺中性白细胞增多,GSK256066水性悬浮液的ED50值为1.1 μg/kg,干粉末制剂的ED50值为2.9 μg/kg,比皮质类固醇丙酸氟替卡松的水性悬浮液更有效,其ED50值为9.3 μg/kg [1]。
临床试验:在慢性阻塞性肺病中度患者中,吸入给药GSK256066的耐受性良好。需要进一步的研究确认其安全性以及化合物的临床疗效[2]。
参考文献:
[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.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 518.58 |
Cas No. | 801312-28-7 |
Formula | C27H26N4O5S |
Solubility | insoluble in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | 6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide |
SDF | Download SDF |
Canonical SMILES | CC1=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 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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 |
质量控制和MSDS
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