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    GSK256066
    GSK256066

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0783
    CAS #: 801312-28-7 Purity ≥98%

    Description: GSK256066 is a novel, potent and selective inhibitor of PDE4B(phosphodiesterase 4B) with IC50 of 3.2 pM, it has >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. GSK256066 can be given 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. 

    References: J Pharmacol Exp Ther. 2011 Apr;337(1):145-54; J Pharmacol Exp Ther. 2011 Apr;337(1):137-44.

    Related CAS: 801315-14-0 (HCl salt); 1415560-64-3 (TFA salt); 801312-28-7 (free base);

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    Molecular Weight (MW)518.58
    FormulaC27H26N4O5S
    CAS No.801312-28-7 (free base); 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 5 mg/mL (9.6 mM)
    Water:<1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL
    SynonymsGSK-256066; GSK 256066; GSK256066;  

    Chemical Name: 6-[[3-[(Dimethylamino)carbonyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methyl-3-quinolinecarboxamide

    InChi Key: JFHROPTYMMSOLG-UHFFFAOYSA-N

    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)

    SMILES Code: 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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    In Vitro

    In vitro activity: GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 × 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity.


    Kinase Assay: GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. IC50 value: 3.2 pM. 


    Cell Assay: GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 × 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity.

    In VivoGSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 ml/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the male CD rat. GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats. GSK256066 (10 μg/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes.
    Animal modelMale CD rats
    Formulation & DosageDissolved in 0.9% sodium chloride solution; 0.1–100 μg/kg; Administered intratracheally as an aqueous suspension or a dry powder 2 h before LPS challenge.
    ReferencesJ Pharmacol Exp Ther. 2011 Apr;337(1):145-54; Bioorg Med Chem Lett. 2009 Sep 1;19(17):5261-5; J Pharmacol Exp Ther. 2011 Apr;337(1):137-44. 


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    GSK256066

    Progress plots showing the time-dependent inhibition of full-length PDE4B by the indicated concentrations of GSK256066 at a cAMP concentration of 8.0 μM. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54. 
     

    GSK256066

    The variation of initial rate (a) and steady-state rate (b) with GSK256066 concentration for full-length PDE4B at cAMP concentrations of i, 0.010 μM; ii, 8.0 μM; iii, 20 μM. J Pharmacol Exp Ther.2011 Apr;337(1):145-54. 
     

    GSK256066

    GSK256006 slowly dissociates from PDE4B. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54. 
     

    GSK256066


    Dose-response curves for the inhibition of LPS-stimulated TNFα by GSK256066 and AWD 12-281 in PBMCs and whole blood. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54. 
     

    GSK256066


    Inhibition of LPS-induced pulmonary neutrophilia in the rat: dose-related inhibition by GSK256066 (○) and FP (▴). J Pharmacol Exp Ther. 2011 Apr;337(1):145-54. 
     

    GSK256066


    LPS-induced pulmonary neutrophilia in rats: effect of GSK256066 after administration as a dry powder 2 h before LPS challenge. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54. 


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