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AM251

现货
Catalog No.
B1427
有效的CB1拮抗剂
组合的产品项目
规格价格库存 数量
5mg
¥ 400.00
现货
10mg
¥ 650.00
现货
50mg
¥ 2,500.00
现货

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Background

AM521 is a potent cannabinoid 1 (CB1) receptor antagonist with IC50 of 8 nM and Ki of 7.49 nM.

The cannabinoid receptor (CB1 and CB2) is a member of G-protein coupled receptor which plays a significant role in physiologic processes such as cognitive and immune functions.

AM251 inhibited the coupling of cannabinoid 1 receptor agonists and antagonists onto the rat brain membranes [1]. In hippocampus, 2 μm AM 251 reduced the endocannabinoids inhibitory effects on GABA release [2]. 1 μm AM 251 inhibited endocannabinoid-signaled depression of interneuron firing [3]. AM251 reduced neuronal excitability and inhibited excitatory and inhibitory transmitter release via inhibition of voltage-dependent Na+ channels [4].

AM251 caused sustained anorectic effect in rat for obesity treatment [5]. AM251 may also disrupt the training – induced increase of hippocampus cannabinoids level that promotes memory consolidation [6].

References:
[1] Lan, R, Q.  Liu, P. Fan, S. Lin, S. R. Fernando, D. McCallion, R. Pertwee & A. Makriyannis: Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J. Med. Chem. 1999, 42, 769–776.
[2] Willow, M.  & W. A. Catterall: Inhibition of binding of [3H]batrachotoxin A 20-α-benzoate to sodium channels by the anticonvulsant drugs diphenylhydantoin and carbamazepine. Mol. Pharmacol. 1982, 22, 627–635.
[3] Kreitzer, A.  C., A. G. Carter & W. G. Regehr: Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 2002, 34, 787–796.
[4] Liao C, Zheng J, David LS, Nicholson RA.  Inhibition of voltage-sensitive sodium channels by the cannabinoid 1 receptor antagonist AM 251 in mammalian brain.  Basic Clin Pharmacol Toxicol. 2004 Feb;94(2):73-8.
[5] Chambers AP, Sharkey KA, Koopmans HS.  Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of daily food intake in the rat.  Physiol Behav.  2004 Oct 15;82(5):863-9.
[6] de Oliveira Alvares L, de Oliveira LF, Camboim C, Diehl F, Genro BP, Lanziotti VB, Quillfeldt JA.  Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats.  Neurobiol Learn Mem. 2005 Mar;83(2):119-24.

Chemical Properties

StorageStore at -20°C
M.Wt555.24
Cas No.183232-66-8
FormulaC22H21Cl2IN4O
Solubility≥55.5mg/mL in DMSO with gentle warming
Chemical Name1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide
SDFDownload SDF
Canonical SMILESCC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)I
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

Caspase-3 试验

巨噬细胞接种(2×106/孔)于12孔培养板,加入DMSO 溶解的4 mM AM-251储备液,1小时后再加入乙醇溶解的2 mg/mL 7-酮基胆固醇,调节对照组,达到等体积的DMSO和乙醇。16小时后,测定caspase-3的活性。所有处理重复3次进行,数据以平均±标准误RFLU/mg蛋白质表示。

细胞实验 [2, 3]:

细胞系

人源黑色素瘤细胞A375; 264.7巨噬细胞

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

5 μM 处理48 h和72 h; 或 0.5、2 μM处理16 h

应用

AM251 (5 μmol/l) 处理黑色素瘤细胞A375,诱导其凋亡、细胞周期停滞G2/M期并且增加cAMP 表达水平;同时,AM-251抑制7-酮基胆固醇介导的264.7巨噬细胞的凋亡。

动物实验 [3]:

动物模型

成年雄性Sprague Dawley大鼠模型

剂量

3 mg/kg,腹腔注射给药,持续1-4小时

应用

AM251处理大鼠增加对氧磷和毒死蜱氧的毒性;同时,AM-251 (1-4 μM)在体内抑制甾醇酯化;AM-251处理来源于野生型与CB2受体敲除小鼠的腹腔巨噬细胞能抑制乙酰化低密度脂蛋白刺激的胆固醇的酯化。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1. Thewke, D., Freeman-Anderson, N., Pickle, T., Netherland, C. and Chilton, C. (2009) AM-251 and SR144528 are acyl CoA:cholesterol acyltransferase inhibitors. Biochem Biophys Res Commun. 381, 181-186

2. Carpi, S., Fogli, S., Romanini, A., Pellegrino, M., Adinolfi, B., Podesta, A., Costa, B., Da Pozzo, E., Martini, C., Breschi, M. C. and Nieri, P. (2015) AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. Anticancer Drugs. 26, 754-762

3. Liu, J. and Pope, C. (2015) The cannabinoid receptor antagonist AM251 increases paraoxon and chlorpyrifos oxon toxicity in rats. Neurotoxicology. 46, 12-18

质量控制

化学结构

AM251