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- GSK256066
GSK256066
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.
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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. |
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Reacting condition |
0.1 pM-1 nM, 20 h |
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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]: | |
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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 |
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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. |
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| Description | GSK256066 is a highly potent and selective inhibitor of phosphodiesterase 4 (PDE4) with IC50 value of 3.2 pM. | |||||
| Targets | PDE4 | |||||
| IC50 | 3.2 pM | |||||
Quality Control & MSDS
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Chemical structure
