GW-311616 是高活性，口服生物相容性，长效的人中性白细胞弹性蛋白酶 (HNE) 抑制剂，IC50为 22 nM，Ki为 0.31 nM。
| 生物活性 | GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophilelastase(HNE) inhibitor withIC50value of 22 nM andKivalue of 0.31 nM[1]. |
| IC50& Target | IC50: 22 nM (HNE)[1]Ki: 0.31 nM (HNE)[1] |
体外研究
(In Vitro) | GW-311616 (150 μM; 48 hours) markedly suppresses NE activity in U937 and K562 cells lines[2].
GW311616A (20-320 μM; 48 hours; U937 cells) treatment inhibits proliferation and induces apoptosis in leukemia cells[2].
GW-311616 (150 μM; U937 cells) treatment can increase the protein expression levels of Bax and decrease the expression of Bcl-2[2].
Cell Viability Assay[2] | Cell Line: | U937 and K562 cells | | Concentration: | 150 μM | | Incubation Time: | 48 hours | | Result: | Markedly suppressed NE activity. |
Apoptosis Analysis[2] | Cell Line: | U937 cells | | Concentration: | 20 μM, 40 μM, 80 μM, 160 μM, 320 μM | | Incubation Time: | 48 hours | | Result: | The rate of apoptosis was enhanced. |
Western Blot Analysis[2] | Cell Line: | U937 cells | | Concentration: | 150 μM | | Incubation Time: | 48 hours | | Result: | Increased the protein expression levels of Bax and decreased the expression of Bcl-2. |
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体内研究
(In Vivo) | GW-311616 (2 mg/kg; oral administration) rapidly abolishes the circulation of neutrophil elastase (NE) in dogs, while >90% inhibition is maintained for 4 days. This prolonged effect is independent to be due to penetration of neutrophils in bone marrow by orally administrated GW-311616. GW-311616 has moderate terminal elimination half-life (t1/2) of 1.1 hours and 1.5 hours for dog (2 mg/kg, oral), rat (2 mg/kg, oral), respectively[3].
| Animal Model: | Dogs (9-month-old)[3] | | Dosage: | 0.22 mg/kg, 0.66 mg/kg and 2 mg/kg (Pharmacokinetic study) | | Administration: | Oral administration | | Result: | At 0.22 mg/kg, greater than 50% inhibition of elastase is achieved 6 hours after dosing, with activity returning towards control values. Single oral dose of 2 mg/kg rapidly abolishes circulating enzyme activity, and greater than 90% inhibition is maintained for 4 days. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(230.42 mM;Need ultrasonic) H2O : 100 mg/mL(230.42 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3042 mL | 11.5210 mL | 23.0420 mL | | 5 mM | 0.4608 mL | 2.3042 mL | 4.6084 mL | | 10 mM | 0.2304 mL | 1.1521 mL | 2.3042 mL |
*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 (sealed storage, away from moisture)。-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: ≥ 2.5 mg/mL (5.76 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.76 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (5.76 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.76 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (5.76 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.76 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 25.0 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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