| 名称 | ARN272 |
| 描述 | ARN272 is a FAAH-like anandamide transporter (FLAT) inhibitor (IC50: 1.8 μM). |
| 动物实验 | All rats were surgically implanted with intra-oral cannula under isoflurane anaesthesia. Following recovery from surgery (3 days), rats received a single adaptation trial to habituate them to the chamber and the infusion procedure. During the adaptation trial, rats were placed individually in the TR chamber and received a 2?min intra-oral infusion of water (reverse osmosis water infused at 1?mL/min). On the following day, rats received the first of two conditioning trials (separated by 72?h). On each conditioning trial, rats received a pretreatment injection of ARN272 or VEH 120?min prior to the conditioning trials. During conditioning trails, rats were intra-orally infused with a saccharin solution (0.1%) for 2?min (1?mL/min) and orofacial and somatic reactions were recorded on video. Immediately following the saccharin infusion, the rats were injected with LiCl (0.15?M) or saline, and then returned to their home cage. Two additional groups were added (after ARN272 at 3.0?mg·kg?1 attenuated gaping) where pretreatment of ARN272 at 3.0?mg·kg?1 or VEH was given 120?min prior, and with SR141716 30?min prior, to each conditioning trial. The groups were VEH-Saline (VEH-SAL), n = 9; VEH-LiCl, n = 8; 0.1?mg/kg ARN272-LiCl, n = 9; 1.0?mg/kg ARN272-LiCl, n = 8; 3.0?mg/kg ARN272-LiCl, n = 8; 1.0?mg/kg SR-3.0?mg/kg ARN272, n = 8; 1.0?mg/kg SR-VEH, n = 8. Seventy-two hours following the second conditioning trial, the rats received a drug-free TR test. During the TR test, rats were re-exposed to a 2?min intra-oral infusion of saccharin solution and their orofacial and somatic responses again recorded. All video recordings were later scored by a rater blind to the experimental conditions using ‘The Observer'. Following the TR test, the rats were returned to their home cages and at 16:00?h, their water bottles were removed to begin a water deprivation regime in preparation for the CTA test.At 08:00?h the following morning, the rats received a one-bottle test in which a graduated tube of 0.1% saccharin solution was placed on the home cage, and the amount consumed was recorded at 30 and 120?min intervals. A one-bottle test was used as there is evidence to suggest it is more sensitive in detecting between-group differences in strength of taste avoidance than a two-bottle test where both water and saccharin are made available [2]. |
| 体外活性 | ARN272对FLAT的抑制似乎是选择性的，因为这种化合物对几种内源性大麻素代谢酶几乎没有或没有抑制作用。此外，ARN272对大鼠脑FAAH活性的抑制作用弱且不完全，且在与重组人FAAH-1孵育后不被显著水解（在37°C下孵育24小时后的水解率约为5%）[1]。 |
| 体内活性 | 在小鼠体内，通过腹腔注射ARN272（1mg/kg）能够提高血浆中阿纳米酰胺（anandamide）的水平，而不影响2-AG、OEA或PEA的水平。研究指出，ARN272抑制阿纳米酰胺在体外内化和在体内失活的效应，以及在faah-1/ 小鼠中观察到的阿纳米酰胺积聚减少现象[1]。ARN272的系统性给药在大鼠中产生了剂量依赖性地抑制因恶心引起的条件性张口行为，并在鼩鼱中减少了呕吐的剂量依赖性降低。在大鼠中，与ARN272（3.0mg/kg）的系统性共同给药能完全逆转ARN272以1.0mg/kg抑制的张口行为。SR141716单独使用的效果与载体溶液无差异[2]。 |
| 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 | H2O : Insoluble
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.62 mM), Sonication is recommended.
Ethanol : 8 mg/mL (18.5 mM), Sonication is recommended.
DMSO : 50 mg/mL (115.61 mM), Sonication is recommended.
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| 关键字 | Inhibitor | inhibit | FAAH | ARN-272 | ARN272 |
| 相关产品 | 2-Chlorophenylboronic acid | Drinabant | AM281 | PF 750 | β-Caryophyllene | Pregnenolone acetate | 2,3-Butanediol | CB1 antagonist 2 | Biochanin A | Dehydroabiethylamine | Pregnenolone | CB2 modulator 1 |
| 相关库 | 抑制剂库 | 脂代谢化合物库 | 经典已知活性库 | 已知活性化合物库 | 代谢化合物库 | 神经信号分子库 | NO PAINS 化合物库 | 抗肥胖化合物库 | GPCR靶点分子库 | 抗代谢疾病化合物库 |
