GSK256066 化学構造
分子量: 518.58




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製品説明 GSK256066は、3.2pMのIC50による選択的なPED4B阻害剤です。
ターゲット PDE4B
IC50 3.2 pM [1]
In vitro試験 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. [1]
In vivo試験 GSK256066 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. [1] 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. [2] 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. [3]
臨床試験 GSK256066 is currently in phase II clinical trials for Chronic Obstructive Pulmonary Disease (COPD)

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

SPA assays and fluorescence polarization assays For SPA assays, 75 μL of PDE enzyme in 50 mM Tris-HCl, pH 7.5, containing 8.3 mM MgCl2, 1.7 mM EGTA, and 0.05% (w/v) BSA is preincubated with 2 μL of GSK256066 solution or DMSO for 30 min. For PDE1 assays the assay buffer containes additionally 4 μg/mL calmodulin and 1 mM CaCl2 and does not contain any EGTA. Assays are initiated by the addition of 25 μL of [3H]cAMP (10 nM final concentration: PDE3, PDE4, and PDE7) or [3H]cGMP (36 nM: PDE1, PDE2, PDE5, and PDE6). After a 1 hour incubation, assays are terminated by addition of 50 μL of aqueous suspension of SPA beads (approximately 1 mg per well) and, after an incubation of at least 30 min, bound radioactivity is measured by liquid scintillation counting. For fluorescence polarization assays, 10 μL of PDE enzyme in 10 mM Tris-HCl buffer, pH 7.2, containing 10 mM MgCl2, 0.1% (w/v) BSA, and 0.05% (w/v) NaN3 is preincubated with 0.5 μL of inhibitor or DMSO for 30 min. Assays are initiated by the addition of 10 μL of fluorescein-cAMP (40 nM final concentration) and terminated after 40 min by the addition of 60 μL of IMAP binding reagent (1 in 400 dilution of stock suspension in binding buffer). The ratio of parallel to perpendicular light is measured using an Analyst or Aquest plate reader.

動物実験: [1]

動物モデル Male CD rats
製剤 Sterile 0.9% sodium chloride solution
投薬量 0.1–100 μg/kg
投与方法 Administered intratracheally as an aqueous suspension or a dry powder 2 h before LPS challenge.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)



Download GSK256066 SDF
分子量 518.58


CAS No. 801312-28-7
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 5 mg/mL (9.64 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 30% propylene glycol, 5% Tween 80, 65% D5W 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 6-(3-(dimethylcarbamoyl)phenylsulfonyl)-4-(3-methoxyphenylamino)-8-methylquinoline-3-carboxamide



電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)


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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID