GSK256066
(Synonyms: 6-[[3-[(二甲基氨基)羰基]苯基]磺酰]-4-[(3-甲氧基苯基)氨基]-8-甲基-3-喹啉甲酰胺) 目录号 : GC14180A potent PDE4 inhibitor
Cas No.:801312-28-7
Sample solution is provided at 25 µL, 10mM.
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.
Cell experiment [1]: | |
Cell lines |
Human peripheral blood mononuclear cells, PBMCs |
Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition |
0.1 pM-1 nM, 20 h |
Applications |
GSK256066 effectively inhibited tumor necrosis factor ɑ (TNFɑ) production by LPS-stimulated PBMCs with IC50 value of 0.01 nM and by LPS-stimulated whole blood with IC50 value of 126 pM.GSK256066 was more potent in both PBMCs and whole blood than other comparator compounds tested. |
Clinical experiment [2]: | |
Clinical samples |
patients aged 40-75 years with chronic obstructive pulmonary disease (COPD) |
Dosage form |
25 mg or 87.5 mg, once daily for 28 days |
Application |
Administration of the potent inhaled PDE4 inhibitor GSK256066 was well-tolerated and did not give rise to gastrointestinal adverse events in patients with moderate COPD. Patients administrated 87.5 mg GSK256066 showed a trend for improvement in lung function and some potential to reduce lung hyperinflation. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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. |
Cas No. | 801312-28-7 | SDF | |
别名 | 6-[[3-[(二甲基氨基)羰基]苯基]磺酰]-4-[(3-甲氧基苯基)氨基]-8-甲基-3-喹啉甲酰胺 | ||
化学名 | 6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide | ||
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 | ||
分子式 | C27H26N4O5S | 分子量 | 518.58 |
溶解度 | <1.04 mg/mL in DMSO, <2.09 mg/mL in EtOH, <2.29 mg/mL in Water | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.9283 mL | 9.6417 mL | 19.2834 mL |
5 mM | 0.3857 mL | 1.9283 mL | 3.8567 mL |
10 mM | 0.1928 mL | 0.9642 mL | 1.9283 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet