GSK356278 是一种有效，选择性，具有口服活性和可透过血脑屏障的磷酸二酯酶 4 (PDE4) 抑制剂，对人 PDE4A，PDE4B 和 PDE4D 的pIC50值分别为 8.6、8.8 和 8.7。GSK356278 具有抗炎活性，并具有抗焦虑和增强认知的作用。
| 生物活性 | GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor ofphosphodiesterase4 (PDE4), withpIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory activity, and exhibits anxiolytic and cognition-enhancing effects[1]. |
| IC50& Target[1] | PDE4A 8.6 (pIC50) | PDE4B 8.8 (pIC50) | PDE4D 8.7 (pIC50) |
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体外研究
(In Vitro) | GSK356278 competes with [3H]rolipram for the high affinity rolipram binding site (HARBS) with a pKiof 8.6 in a competitive filtration-binding assay to the recombinant human PDE4B2B enzyme expressed in yeast membranes[1].
GSK356278 bounds to the HARBS in rats, mice, marmosets, and ferrets with pKis of 7.9, 7.8, 8.4, and 8.5, respectively[1].
GSK356278 inhibits LPS-induced release of TNF-α in human whole blood, with a pIC50of 7.6[1].
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体内研究
(In Vivo) | GSK356278 (0.003-30 mg/kg; p.o.) shows anti-inflammatory activity in rodents at exposures that does not induce pica feeding[1].
GSK356278 (0.1-0.1 mg/kg; p.o.) demonstrates efficacy in a nonhuman primate model of anxiety at exposures that do not induce emesis[1].
GSK356278 (4 doses at 0.03, 0.1, 0.3, and 1.0 mg/kg for 6 weeks; p.o.) enhances performance in a nonhuman primate object retrieval test[1].
GSK356278 exhibits oral bioavailability (rat 91%, monkey 23%) and Cmax(rat 205, monkey 41 nM) following oral administration (rat 1, monkey 0.2 mg/kg)[1].
GSK356278 exhibits terminal elimination half-lives (rat 2.2, monkey 1.5 h) due to moderate blood clearance (rat 40, monkey 16 mL/min/kg) combined with volumes of distribution (rat 6.3, monkey 2.1 L/kg) following intravenous administration (rat 1, monkey 0.2 mg/kg)[1].
| Animal Model: | Male Lewis rats (320-400 g) are treated with lipopolysaccharide (LPS)[1] | | Dosage: | 0.003-3 mg/kg | | Administration: | P.o. administration 30 minutes prior to the LPS challenge | | Result: | Reduced the level of neutrophilia in a dose-dependent manner, with an ED50of 0.09 mg/kg. |
| Animal Model: | Male CD rats[1] | | Dosage: | 1 mg/kg (Pharmacokinetic Analysis) | | Administration: | I.v. and p.o. administration | | Result: | Oral bioavailability (91%), Cmax(205 nM), T1/2(2.2 h). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 2.5 mg/mL(5.69 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.2752 mL | 11.3758 mL | 22.7516 mL | | 5 mM | 0.4550 mL | 2.2752 mL | 4.5503 mL | | 10 mM | --- | --- | --- |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 1.25 mg/mL (2.84 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (2.84 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 1.25 mg/mL (2.84 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (2.84 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 1.25 mg/mL (2.84 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (2.84 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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