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Purity: ≥98%
GSK256066 (GSK-256066; GSK 256066) is a novel, potent and selective inhibitor of PDE4B (phosphodiesterase 4B) with important biological activity (e.g. inhibiting pulmonary neutrophilia). It inhibits PDE4B with an IC50 of 3.2 pM, and has >380,000-fold selectivity for PDE4B over PDE1/2/3/5/6. GSK256066 can be administered by inhalation which can minimize the potential for side effects. It demonstrated a protective effect on the EAR and LAR. GSK256066 has been demonstrated to have exceptional potency in vitro and in vivo and is being clinically investigated as a treatment for chronic obstructive pulmonary disease.
| ln Vitro |
One PDE4 inhibitor with a particularly high affinity for inhaled administration is GSK256066 [1]. PDE4 is highly selective for GSK256066; it is 380,000 times more selective than PDE1/2/3/5/ and 2500 times more selective than PDE7 [1]. The same amount of PDE4 isoform AD (PDE4B: pIC50≥11.5, PDE4A: pIC50≥11.31, PDE4C: pIC50≥11.42, PDE4D: pIC50≥11.94) is inhibited by GSK256066 [1]. GSK256066 inhibits human peripheral blood mononuclear cells' production of TNF-α when they are stimulated by lipopolysaccharide (LPS) at an IC50 of 0.01 nM[1].
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| ln Vivo |
Significant inhibition of LPS-induced lung neutrophilia is observed with GSK256066 (10 μg/kg) [2]. Moreover, LPS-induced increases in exhaled nitric oxide (ED50 = 92 μg/kg) are inhibited by GSK256066[2]. In rats exposed to ovalbumin (ED50=0.4 μg/kg), GSK256066 prevents eosinophilia in the lungs[2].
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| Animal Protocol |
Animal/Disease Models: Male Brown Norway rats (180-200 g)[2]
Doses: 10 μg/kg Route of Administration: Intracheal injection; before (36 hrs (hours), 24 hrs (hours), 18 hrs (hours), 12 hrs (hours), 6 hrs (hours), and 2 hrs (hours)) and after (0 hour, 2 hrs (hours)) LPS challenge Experimental Results: Inhibited the LPS-induced pulmonary neutrophilia. |
| References |
[1]. Tralau-Stewart CJ, 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 Pharmacol Exp Ther, 2011, 337(1), 145-154.
[2]. Nials AT, et al. In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitor. J Pharmacol Exp Ther, 2011, 337(1), 137-144. |
| Molecular Formula |
C27H26N4O5S
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| Molecular Weight |
518.58
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| CAS # |
801312-28-7
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| Related CAS # |
GSK256066 Trifluoroacetate;1415560-64-3
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| SMILES |
O=C(C1=C(NC2=CC=CC(OC)=C2)C3=CC(S(=O)(C4=CC=CC(C(N(C)C)=O)=C4)=O)=CC(C)=C3N=C1)N
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| InChi Key |
JFHROPTYMMSOLG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H26N4O5S/c1-16-11-21(37(34,35)20-10-5-7-17(12-20)27(33)31(2)3)14-22-24(16)29-15-23(26(28)32)25(22)30-18-8-6-9-19(13-18)36-4/h5-15H,1-4H3,(H2,28,32)(H,29,30)
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| Chemical Name |
6-[[3-[(Dimethylamino)carbonyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methyl-3-quinolinecarboxamide
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| Synonyms |
GSK-256066; GSK 256066; GSK256066;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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