| 名称 | ABX-1431 |
| 描述 | ABX-1431 (Elcubragistat) is a selective and orally available CNS-penetrant monoacylglycerol lipase (MAGL/MGLL) inhibitor (IC50: 14 nM). |
| 细胞实验 | Human prostate cancer PC3 cells were grown in F-12K medium supplemented with 10% fetal bovine serum at 37°C with 5% CO2 to ~80% confluency in 100 mm dishes. ABX-1431 was added to cells to give final concentration of 0.1–10 μM compound in serum free media. Cells were incubated with compound for 30 min at 37°C with 5% CO2. Cells were washed, harvested, and lysed by probe sonication. Cell lysates (2mg/mL) were treated with JW912 (1μM) and analyzed by SDS-PAGE and in-gel fluorescence scanning. |
| 动物实验 | All animals were 6?8 weeks old at the time of study and weighed between 197-217 g. Animals (n = 3 per dosing route) were dosed with ABX-1431 at 1 mg/kg iv (in 70% polyethylene glycol (PEG) 400 in hydroxypropyl-?-cylcodextran (HPBCD) in saline) or 5 mg/kg po (in 70% PEG 400 in 0.5% carboxymethylcellulose (CMC, w/v) in saline). Animals were fasted overnight, and food withheld until 4 h post dose. Approximately 100 μL of blood were collected via a jugular vein catheter at 0.033, 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h after intravenous and 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h after oral administration. All blood samples were collected into tubes containing 400 μL acetonitrile to immediately inactivate blood esterase activity and frozen at ?80 °C. Samples were thawed and centrifuged (14,000 rpm for 5 min at 4 °C) and the supernatant transferred for LCMS analysis. |
| 体外活性 | ABX-1431是一种强效的人类MGLL抑制剂（平均IC50值为0.014 μM），对ABHD6具有超过100倍的选择性，对PLA2G7具有超过200倍的选择性。在对完整的人类PC3细胞进行处理时，经过30分钟的抑制剂孵育之后，ABX-1431对MGLL活性产生了浓度依赖性的抑制，其IC50值为0.0022 μM，约为体外观察到的效力的6倍。在细胞基础实验中，维持了对MGLL超过100倍的选择性，相比之下，ABHD6的IC50值为0.253 μM，PLA2G7的IC50值为494 μM。 |
| 体内活性 | 在体内，ABX-1431抑制啮齿动物脑内的MGLL活性（ED50=0.5-1.4 mg/kg），提高脑内2-AG浓度，并在大鼠甲醛疼痛模型中抑制疼痛行为。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : 10 mg/mL (19.71 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween-80+45% Saline : 2.5 mg/mL (4.93 mM), Sonication is recommeded.
DMSO : 55 mg/mL (108.4 mM), Sonication is recommended.
H2O : Insoluble
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| 关键字 | Monoacylglycerol lipase | MAGL | Inhibitor | inhibit | ABX-1431 | ABX1431 | ABX 1431 |
| 相关产品 | Lipase, triacylglycerol | MJN110 | euphol | Endothelial lipase inhibitor-1 | XEN445 | KT203 | Atglistatin | JJKK 048 | NG-497 | KT182 | Beta-Sitosterol | WWL123 |
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