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
AM251是一种 1 型大麻素受体 (CB1) 拮抗剂，IC50为8nM，同时也是G蛋白偶联受体55 (GPR55) 激动剂，其EC50为39nM。
Cas No.:183232-66-8
Sample solution is provided at 25 µL, 10mM.
AM251 is a cannabinoid receptor type 1 (CB1) antagonist with an IC50 of 8nM and a G protein-coupled receptor 55 (GPR55) agonist with an EC50 of 39nM[1] [2]. AM251 plays an important role in physiological processes such as cognition and immune function, and may be potentially valuable in the prevention and mitigation of fibrosis.
AM251 (10μM, 24hours) suppressed epithelial-mesenchymal transition of renal tubular epithelial cells without cytotoxicity[3]. AM251 (10μM, 48hours) had an inhibitory effect on fibroblasts differentiation into myofibroblasts and collagen production induced by TGF-β in primary human fibroblasts cultures, with a pIC50 of 5.5[4]. AM251 (IC50: 5μmol/L) induced apoptosis and G2/M cell cycle arrest in A375 human melanoma cells[5].
AM251 (3mg/kg, i.p) treatment led to an increase in pro-inflammatory cytokines in rats, while decreasing fat pad mass and altering plasma hormone levels, inducing weight loss and adiposity reduction[6]. AM251 (1mg/kg, i.p.) improved recognition memory in rats without alteration of their psychomotor activity and anxiety[7]. AM251 (1mg/kg, i.p.) attenuated ataxia-related deficits in a cerebellar ataxia model, improved motor activity and blocked Purkinje cells neuronal degeneration in ataxic animals[8].
References:
[1] Bruno A, Lembo F, Novellino E, Stornaiuolo M, Marinelli L. Beyond radio-displacement techniques for identification of CB1 ligands: the first application of a fluorescence-quenching assay. Sci Rep. 2014 Jan 20;4:3757. doi: 10.1038/srep03757. PMID: 24441508; PMCID: PMC3895875.
[2] Sharir H, Abood ME. Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacol Ther. 2010 Jun;126(3):301-13. doi: 10.1016/j.pharmthera.2010.02.004. Epub 2010 Mar 16. PMID: 20298715; PMCID: PMC2874616.
[3] Yoshinaga T, Uwabe K, Naito S, Higashino K, Nakano T, Numata Y, Kihara A. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells. PLoS One. 2016 Dec 9;11(12):e0167848. doi: 10.1371/journal.pone.0167848. PMID: 27936102; PMCID: PMC5148003.
[4] Correia-Sá IB, Carvalho CM, Serrão PV, Machado VA, Carvalho SO, Marques M, Vieira-Coelho MA. AM251, a cannabinoid receptor 1 antagonist, prevents human fibroblasts differentiation and collagen deposition induced by TGF-β - An in vitro study. Eur J Pharmacol. 2021 Feb 5;892:173738. doi: 10.1016/j.ejphar.2020.173738. Epub 2020 Nov 19. PMID: 33220269.
[5] Carpi S, Fogli S, Romanini A, Pellegrino M, Adinolfi B, Podestà A, Costa B, Da Pozzo E, Martini C, Breschi MC, Nieri P. AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. Anticancer Drugs. 2015 Aug;26(7):754-62. doi: 10.1097/CAD.0000000000000246. PMID: 25974027.
[6] O'Keefe L, Vu T, Simcocks AC, Jenkin KA, Mathai ML, Hryciw DH, Hutchinson DS, McAinch AJ. CB1 Ligand AM251 Induces Weight Loss and Fat Reduction in Addition to Increased Systemic Inflammation in Diet-Induced Obesity. Int J Mol Sci. 2022 Sep 28;23(19):11447. doi: 10.3390/ijms231911447. PMID: 36232744; PMCID: PMC9569643.
[7] Bialuk I, Winnicka MM. AM251, cannabinoids receptors ligand, improves recognition memory in rats. Pharmacol Rep. 2011;63(3):670-9. doi: 10.1016/s1734-1140(11)70578-3. PMID: 21857077.
[8] Ranjbar H, Soti M, Kohlmeier KA, Sheibani V, Ahmadi-Zeidabadi M, Rafiepour K, Shabani M. The cannabinoid antagonist, AM251 attenuates ataxia related deficiencies in a cerebellar ataxic model. Int J Neurosci. 2024 May;134(5):522-529. doi: 10.1080/00207454.2022.2126771. Epub 2022 Sep 30. PMID: 36120979.
AM251是一种 1 型大麻素受体 (CB1) 拮抗剂，IC50为8nM，同时也是G蛋白偶联受体55 (GPR55) 激动剂，其EC50为39nM[1] [2]。AM251在认知和免疫功能等生理过程中发挥重要作用，在预防和缓解纤维化方面可能具有潜在价值。
AM251 (10μM，24hours) 可抑制肾小管上皮细胞的上皮-间质转化，且无细胞毒性[3]。AM251 (10μM，48hours) 对原代人成纤维细胞培养物中由TGF-β诱导的成纤维细胞向肌成纤维细胞分化和胶原生成具有抑制作用，pIC50为5.5[4]。AM251 (IC50：5μmol/L) 可诱导A375人黑色素瘤细胞凋亡和G2/M细胞周期停滞[5]。
AM251 (3mg/kg, i.p) 可导致大鼠体内促炎细胞因子增加，同时减少脂肪垫质量并改变血浆激素水平，诱导体重下降和脂肪减少[6]。AM251 (1mg/kg, i.p.) 可改善大鼠的识别记忆，但不会改变其精神运动活动和焦虑[7]。AM251 (1mg/kg, i.p.) 可减轻小脑共济失调模型中与共济失调相关的缺陷，改善共济失调动物的运动活动并阻止Purkinje细胞神经元变性[8]。
| Cell experiment [1]: | |
Cell lines | Renal tubular epithelial cell line HK-2 |
Preparation Method | HK-2 cells were plated at 2 × 104 cells per well on poly-D-lysine-coated 96-well plates overnight. TGF-β1 (2ng/ml) and AM251 (10μM) were incubated with the cells for 24h. |
Reaction Conditions | 10μM, 24hours |
Applications | AM251 inhibited epithelial-mesenchymal transition in renal tubular epithelial cells, which informed the development of a novel therapeutic agent that inhibited EMT thereby preventing renal fibrosis. |
| Animal experiment [2]: | |
Animal models | Male Sprague Dawley rats |
Preparation Method | Following the acclimatization period rats receive a high-fat diet (HFD) containing 40% digestible energy from lipids for 9 weeks. Animals were then maintained on the HFD and treated for a further six weeks with a daily i.p. injection, with 3mg/kg body weight of AM251 dissolved in the vehicle solution. Following treatment, rats were anesthetized with 3% isoflurane inhalation with each animal undergoing surgical removal of skeletal muscle, cardiac blood was then collected confirming death, with all other major organs including fat pads were removed post-mortem, weighed, and stored at −80 °C for further analyses. |
Dosage form | 3mg/kg, i.p., 6weeks |
Applications | AM251 induced weight loss and fat reduction in addition to increased systemic inflammation in diet-induced obesity, the administration of AM251 increased systemic inflammation with increased levels of a wide range of cytokines. |
References: [1] Yoshinaga T, Uwabe K, Naito S, Higashino K, Nakano T, Numata Y, Kihara A. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells. PLoS One. 2016 Dec 9;11(12):e0167848. doi: 10.1371/journal.pone.0167848. PMID: 27936102; PMCID: PMC5148003. | |
| 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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