GSK256066 |
| Katalog-Nr.GC14180 |
A potent PDE4 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 801312-28-7
Sample solution is provided at 25 µL, 10mM.
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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]: | |
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Cell lines |
Human peripheral blood mononuclear cells, PBMCs |
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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) |
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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. |
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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. |
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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 | |
| Chemical Name | 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 | ||
| Formula | C27H26N4O5S | M.Wt | 518.58 |
| Löslichkeit | <1.04 mg/mL in DMSO, <2.09 mg/mL in EtOH, <2.29 mg/mL in Water | Storage | Store at -20°C,unstable in solution, ready to use. |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9283 mL | 9.6417 mL | 19.2834 mL |
| 5 mM | 385.7 μL | 1.9283 mL | 3.8567 mL |
| 10 mM | 192.8 μL | 964.2 μL | 1.9283 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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