AVE-3085
目录号 : GC32486
AVE-3085是一种有效的nitricoxidesynthase增强剂，常用于治疗心血管疾病。
Cas No.:450348-85-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Male C57BL/6J mice (8-10 weeks old; 24-26 g) are housed in individual cages on a 12 h light-dark cycle in a temperature- (24 ± 2°C) and humidity-controlled room with ad libitum access to tap water and standard rodent chow. The mice are anesthetized via an intraperitoneal injection of 1.5% pentobarbital (W*0.06), and cardiac hypertrophy is induced by pressure overload, which is achieved via descending aortic banding (AB). Similar surgeries that do not include aortic banding are performed on the sham-operated. Twenty-four hours after ligation, the surviving mice are randomly divided into the following three groups (n=8 per group): (1) a sham-operated group (Sham group), (2) a vehicle-treated AB group (vehicle-treated group), and (3) an AB group treated with AVE 3085 (AVE 3085 group). AVE 3085 is administered orally once daily at a dose of 10 mg kg day−1 for 4 weeks, and isovolumic sodium chloride is administered in the same manner to the sham-operated and vehicle-treated groups. |
References: [1]. Chen Y, et al. AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway. Arch Biochem Biophys. 2015 Mar 15;570:8-13. | |
AVE-3085 is a potent endothelial nitric oxide synthase enhancer, used for cardiovascular disease treatment.
Pre-incubation with AVE3085 restores the bradykinin-induced relaxation, reverses the decrease of p-eNOSSer1177, and loares the level of p-eNOSThr495 and nitrotyrosine. NO release in response to bradykinin is significantly reduced by ADMA and such reduction is restored by AVE3085. AVE3085 also prevents the elevation of O2.- and ONOO- levels in coronary arteries exposed to ADMA[2]. AVE3085 (10 μM) markedly increases ACh-induced relaxations in SHR aortae without affecting those in WKY aortae, and also increases the eNOS expression in WKY aortae[3].
AVE 3085 (10 mg/kg/day, p.o.) treatment prevents the increases in the left ventricular weight, left ventricular weight/body weight ratio, mean myocyte diameter, and the expression of the hypertrophic markers ANP and β-MHC compared to the vehicle-treated mice. AVE 3085 treatment also attenuates the collagen volume fraction levels compared to the vehicle-treated mice. In the AVE 3085-treated mice, the EFs, FSs, mitral E velocity, E/A ratio and LVDds are significantly improved compared to the vehicle-treated mice. AVE 3085 treatment attenuates the increase in the expression of Smad2 mRNA. Furthermore, the levels of the eNOS protein expression are significantly up-regulated in the AVE 3085 group than in the vehicle-treated AB group[1]. AVE3085 (10 mg/kg, p.o.) significantly improves ACh-induced endothelium-dependent relaxations in the aortae of SHRs, and reduces systolic blood pressure in SHRs. AVE3085 treatment for 4 weeks increases levels of p-eNOS and eNOS in SHR aortae without affecting levels of eNOS and p-eNOS in WKY aortae[3].
[1]. Chen Y, et al. AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway. Arch Biochem Biophys. 2015 Mar 15;570:8-13. [2]. Xue HM, et al. AVE3085 protects coronary endothelium from the impairment of asymmetric dimethylarginine by activation and recoupling of eNOS. Cardiovasc Drugs Ther. 2012 Oct;26(5):383-92. [3]. Yang Q, et al. AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats. Br J Pharmacol. 2011 Jul;163(5):1078-85
| Cas No. | 450348-85-3 | SDF | |
| Canonical SMILES | O=C(C1=CC=C(OC(F)(F)O2)C2=C1)NC3CC4=C(C=CC=C4)C3 | ||
| 分子式 | C17H13F2NO3 | 分子量 | 317.29 |
| 溶解度 | DMSO : 250 mg/mL (787.92 mM; Need ultrasonic) | 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 | 3.1517 mL | 15.7585 mL | 31.5169 mL |
| 5 mM | 0.6303 mL | 3.1517 mL | 6.3034 mL |
| 10 mM | 0.3152 mL | 1.5758 mL | 3.1517 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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1. 首先保证母液是澄清的；
2.
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AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway
Arch Biochem Biophys 2015 Mar 15;570:8-13.PMID:25712222DOI:10.1016/j.abb.2015.02.020.
AVE 3085 is a novel endothelial nitric oxide synthase enhancer. Although AVE 3085 treatment has been shown to be effective in spontaneously restoring endothelial function in hypertensive rats, little is known about the effects and mechanisms of AVE 3085 with respect to cardiac remodeling. The present study was designed to examine the effects of AVE 3085 on cardiac remodeling and the mechanisms underlying the effects of this compound. Mice were subjected to aortic banding to induce cardiac remodeling and were then administered AVE 3085 (10 mg kg day(-1), orally) for 4 weeks. At the end of the treatment, the aortic banding-treated mice exhibited significant elevations in cardiac remodeling, characterized by an increase in left ventricular weight relative to body weight, an increase in the area of collagen deposition, an increase in the mean myocyte diameter, and increases in the gene expressions of the hypertrophic markers atrial natriuretic peptide (ANP) and β-MHC. These indexes were significantly decreased in the AVE 3085-treated mice. Furthermore, AVE 3085 treatment reduced the expression and activation of the Smad signaling pathway in the aortic banding-treated mice. Our data showed that AVE 3085 attenuated cardiac remodeling, and this effect was possibly mediated through the inhibition of Smad signaling.
AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats
Br J Pharmacol 2011 Jul;163(5):1078-85.PMID:21385179DOI:10.1111/j.1476-5381.2011.01308.x.
Background and purpose: Nitric oxide (NO) plays an important role in endothelial function, and impaired NO production is involved in hypertension. Therefore, compounds that regulate endothelial NO synthase (eNOS) may be of therapeutic benefit. A novel, low molecular weight compound AVE3085 is a recently developed compound with the ability to enhance eNOS transcription. The present study investigated the effects of AVE3085 in endothelial dysfunction associated with hypertension. Experimental approach: Spontaneously hypertensive rats (SHRs) were treated with AVE 3085 (10 mg·kg·day(-1) , orally) for 4 weeks. Isometric force measurement was performed on rings of isolated aortae in organ baths. Protein expression of eNOS, phosphorylated-eNOS and nitrotyrosine in the aortae were examined by Western blotting. mRNA for eNOS in rat aortae were examined by reverse-transcriptase polymerase chain reaction (RT-PCR). Key results: AVE3085 greatly improved endothelium-dependent relaxations in the aortae of SHRs. This functional change was accompanied by up-regulated expression of eNOS protein and mRNA, enhanced eNOS phosphorylation and decreased formation of nitrotyrosine. Furthermore, AVE3085 treatment reduced the blood pressure in SHR without affecting that of hypertensive eNOS(-/-) mice. Conclusions and implications: The eNOS-transcription enhancer AVE3085 restored impaired endothelial function in a hypertensive model. The present study provides a solid basis for the potential development of eNOS-targeting drugs to restore down-regulated eNOS, as a new strategy in hypertension.