KML29 是高度选择性的、具有口服活性的、不可逆的MAGL抑制剂,其对小鼠、大鼠和人的IC50值分别为15 nM、43 nM 和 5.9 nM。KML29对FAAH在内的其他中心和外周丝氨酸水解酶的交叉反应极小。
生物活性 | KML29 is an extremely selective, orally active and irreversibleMAGLinhibitor, withIC50values of 15 nM, 43 nM and 5.9 nM for mouse, rat and humanMAGL, respectively. KML29 exhibits minimal cross-reactivity toward other central and peripheral serinehydrolases, including no detectable activity againstFAAH[1][2]. |
IC50& Target | IC50: 15 nM (mouse MAGL), 43 nM (rat MAGL), 5.9 nM (human MAGL)[2]. |
体外研究 (In Vitro) | KML29 dose-dependently elevates brain 2-AG level up to 10-fold without alteration in brain levels of anandamide, palmitoylethanolamide, and oleoylethanolamide[2]. KML29 is a potent inhibitor of 2-AG hydrolysis, but did not affect AEA hydrolysis at any concentration tested[2].
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体内研究 (In Vivo) | KML29 enhibits antinociceptive activity without cannabimimetic side effects[3]. KML29 (20 mg/kg) has a significant but modest protective effect against LPS-induced fever[3].
Animal Model: | C57Bl/6 mice[2]. | Dosage: | 1-40 mg/kg. | Administration: | P.O. single dose. | Result: | Selectively inhibited MAGL in mice. |
Animal Model: | Wistar albino male rats[2]. | Dosage: | 20 mg/kg (+LPSE. coliO111:B4 (250 μg/kg, sc)). | Administration: | SC. | Result: | Administration of KML29 simultaneously with LPSE. coliO111:B4 significantly decreased ?T (with 5% type 1 error, 1.7 fold) compared to saline+LPSE. coliO111:B4. Administration of KML29 simultaneously with LPSE. coliO111:B4 resulted in decreased plateau phase of fever compared to LPS E.E. coliO111:B4+saline administration. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 50 mg/mL(91.01 mM;Need ultrasonic) 配制储备液 1 mM | 1.8201 mL | 9.1005 mL | 18.2010 mL | 5 mM | 0.3640 mL | 1.8201 mL | 3.6402 mL | 10 mM | 0.1820 mL | 0.9101 mL | 1.8201 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。-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 (4.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.55 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%corn oil Solubility: ≥ 2.5 mg/mL (4.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.55 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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