AVE-8134
目录号 : GC31452
AVE-8134是PPARα的有效激动剂，对人体和啮齿类动物的PPARα的EC50值分别为100和3000nM。
Cas No.:304025-09-0
Sample solution is provided at 25 µL, 10mM.
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AVE-8134 is a potent PPARα agonist, with EC50 values of 100 and 3000 nM for human and rodent PPARα receptor, respectively.
AVE8134 is a full PPARα dominated PPAR agonist, but not active on PPARδ[1]. In HUVEC, AVE8134 (1 μM) increases Ser-1177-eNOS phosphorylation but not eNOS expression. In monocytes, AVE8134 (10 μM) increases the expression of CD36 and the macrophage scavenger receptor 1, resulting in enhanced uptake of oxidized LDL[2].
In female hApo A1 mice, AVE8134 (130 mg/kg/d, po for 12 d) dose-dependently loweres the plasma triglycerides, and increases the serum HDL-cholesterol, hApo A1 and mouse Apo E levels. In female ZDF rats, AVE8134 (3-30 mg/kg/d for 2 weeks) improves insulin-sensitivity index. In pre-diabetic male ZDF rats, AVE8134 (10 mg/kg/d for 8 weeks) produces an anti-diabetic action comparable to rosiglitazone, without the PPARγ mediated adverse effects on body weight and heart weight. In male ZDF rats, AVE8134 (20 mg/kg/d for 12 weeks) increases mRNA levels of the target genes LPL and PDK4 about 20 fold in the liver, and there is no relevant effect with rosiglitazone[1]. In post-MI rats, AVE8134 (3 mg/kg and 10 mg/kg) dose-dependently improves cardiac output, myocardial contractility and relaxation and reduces lung and left ventricular weight and fibrosis. Treatment at AVE8134 decreases plasma proBNP and arginine and increases plasma citrulline and urinary NOx/creatinine ratio. In DOCA rats, AVE8134 (3 mg/kg/d) prevents development of high blood pressure, myocardial hypertrophy and cardiac fibrosis, and ameliorates endothelial dysfunction. In old SHR, treatment with a low dose of AVE8134 (0.3 mg/kg/d) improves cardiac and vascular function and increases life expectancy without lowering blood pressure. AVE8134 reduces phenylephrine-induced hypertrophy in adult rat cardiomyocytes[2].
[1]. Schafer HL, et al. AVE8134, a novel potent PPARα agonist, improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats. Acta Pharmacol Sin. 2012 Jan;33(1):82-90. [2]. Linz W, et al. The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist, AVE8134, attenuates the progression of heart failure and increases survival in rats. Acta Pharmacol Sin. 2009 Jul;30(7):935-46.
Animal experiment: | Male ZDF rats are treated for 8 weeks. Food consumption and body weight are measured twice a week. The amount of diet for an additional control group is restricted to levels below the estimated consumption of the AVE8134 group: the starting value is 7 g chow/100 g body weight for the first week and than adapted to 8 g/100 g body weight. The chow for that control group is divided into two portions and is offered twice daily when light is switched on and off, all other groups had free access to food, except before measurements of fasted blood glucose, insulin and before oral glucose tolerance test. After two weeks of treatment an oral glucose tolerance test (oGTT) is performed. Briefly, after an overnight fast, the animals are treated with the drugs or vehicle between 06:30 and 07:00, glucose (2 g/kg) is administered orally 2 h later in a volume of 5 mL/kg, blood is drawn from the tip of the tail from using glass capillaries at 0, 30, 60, 90, 120, and 180 min after glucose administration. The glycemic index (GI) is calculated as area under the curve (AUC) of glucose response during oGTT. Blood glucose concentration before oral glucose load (0 min) is defined as baseline of AUC calculation. |
References: [1]. Schafer HL, et al. AVE8134, a novel potent PPARα agonist, improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats. Acta Pharmacol Sin. 2012 Jan;33(1):82-90. | |
| Cas No. | 304025-09-0 | SDF | |
| Canonical SMILES | O=C(O)C1=C(COCCCOCC2=COC(C3=CC=CC=C3)=N2)C=CC=C1C | ||
| 分子式 | C22H23NO5 | 分子量 | 381.42 |
| 溶解度 | Soluble in DMSO | 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 | 2.6218 mL | 13.1089 mL | 26.2178 mL |
| 5 mM | 0.5244 mL | 2.6218 mL | 5.2436 mL |
| 10 mM | 0.2622 mL | 1.3109 mL | 2.6218 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。
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Quality Control & SDS
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- Purity: >98.00%
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