GSK256066

製品コードS2620 バッチS262001

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H26N4O5S
分子量 518.58 CAS No. 801312-28-7
Solubility (25°C)* 体外 4-Methylpyridine (warmed with 50ºC water bath) 11 mg/mL (21.21 mM)
DMSO Insoluble
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
30%propylene glycol 5%Tween80 65%D5W
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.Phase 2.
in vitro 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 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]

プロトコル(参考用のみ)

キナーゼアッセイ 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 動物モデル Male CD rats
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.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Acute Lung Functional and Airway Remodeling Effects of an Inhaled Highly Selective Phosphodiesterase 4 Inhibitor in Ventilated Preterm Lambs Exposed to Chorioamnionitis [ Pharmaceuticals (Basel), 2022, 16(1)29] PubMed: 36678525
Detrimental Effects of an Inhaled Phosphodiesterase-4 Inhibitor on Lung Inflammation in Ventilated Preterm Lambs Exposed to Chorioamnionitis Are Dose Dependent. [ J Aerosol Med Pulm Drug Deliv, 2019, 32(6):396-404] PubMed: 31573405

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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