AM251
(Synonyms: 1-(2,4-二氯苯基)-5-(4-碘苯基)-4-甲基-N-(哌啶-1-基)-1H-吡唑-3-甲酰胺) 目录号 : GC15717
A CB1 receptor antagonist
Cas No.:183232-66-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Caspase-3 assay |
Macrophages are seeded (2 × 106/well) in 12-well culture plates. AM-251 are added from 4 mM stock solutions prepared in DMSO, 1 hour prior to the addition of 7-ketocholesterol from a 2 mg/mL ethanol stock solution. Controls are adjusted to receive equivalent volumes of DMSO and ethanol. After 16 hours, caspase-3 activity is determined. All treatments are done in triplicate and the data presented as the mean RFLU/mg protein± SD. |
| Cell experiment [2, 3]: | |
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Cell lines |
A375 human melanoma cells; Raw 264.7 macrophages |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
5 μM for 48 h and 72 h; or 0.5, 2 μM for 16 h |
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Applications |
Treatment with AM251 (5 μmol/l) induced apoptosis, G2/M cell cycle arrest, and cAMP increase in A375 human melanoma cells. Moreover, AM-251 inhibited 7-ketocholesterol induced apoptosis of Raw 264.7 macrophages. |
| Animal experiment [3]: | |
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Animal models |
Adult male Sprague-Dawley rats model |
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Dosage form |
3 mg/kg, i.p., for 1-4 h |
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Applications |
AM251 increased paraoxon and chlorpyrifos oxon toxicity in rats. Moreover, AM-251 (1-4 μM) inhibited sterol esterification in vivo. AM-251 inhibited acetylated LDL-stimulated cholesterol esterification in resident peritoneal macrophages from wild type and CB2 null mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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 |
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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.
| Cas No. | 183232-66-8 | SDF | |
| 别名 | 1-(2,4-二氯苯基)-5-(4-碘苯基)-4-甲基-N-(哌啶-1-基)-1H-吡唑-3-甲酰胺 | ||
| 化学名 | 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide | ||
| Canonical SMILES | CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)I | ||
| 分子式 | C22H21Cl2IN4O | 分子量 | 555.24 |
| 溶解度 | ≥ 55.5mg/mL in DMSO with gentle warming | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.801 mL | 9.0051 mL | 18.0102 mL |
| 5 mM | 0.3602 mL | 1.801 mL | 3.602 mL |
| 10 mM | 0.1801 mL | 0.9005 mL | 1.801 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。