Etomoxir|124083-20-1|(乙莫克舍; (R)-(+)-Etomoxir)-陌孚医药/Medlife

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Etomoxir (Synonyms: 乙莫克舍; (R)-(+)-Etomoxir)

目录号: PC12451 纯度: ≥98%

CAS No. :124083-20-1

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中文名称	Etomoxir
中文别名	乙莫克舍
英文名称	Etomoxir
英文别名	2-Oxiranecarboxylicacid, 2-[6-(4-chlorophenoxy)hexyl]-, ethyl ester, (2R)-;Etomoxir;R-(+)-Etomoxir;(R)-(+)-Etomoxir;(2R)-2-[6-(4-Chlorophenoxy)hexyl]-2-oxiranecarboxylic acid ethyl ester;S-(+)-ETOMOXIR;ethyl (2S)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate;(R)-2-[6-(4-CHLOROPHENOXY)HEXYL]OXIRANECARBOXYLIC ACID, ETHYL ESTER;(S)-2-[6-(4-CHLOROPHENOXY)HEXYL]OXIRANECARBOXYLIC ACID, ETHYL ESTER;(R)-2-[6-(4-Chlorophenoxy)hexyl]oxirane-2-carboxylic acid ethyl ester;(2S)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylic acid ethyl ester;2-Oxiranecarboxylic acid, 2-[6-(4-chlorophenoxy)hexyl]-, ethyl ester, (2R)-(R)-(+)-Etomoxir;2-Oxiranecarboxylic acid, 2-[6-(4-chlorophenoxy)hexyl]-, ethyl ester, (2R)-
Cas No.	124083-20-1
分子式	C₁₇H₂₃O₄Cl
分子量	326.82
包装储存	-20°C, protect from light, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

生物活性	Etomoxir ((R)-(+)-Etomoxir) is an irreversible inhibitor of carnitine palmitoyltransferase 1a (CPT-1a), inhibits fatty acid oxidation (FAO) through CPT-1a and inhibits palmitate β-oxidation in human, rat and guinea pig.
性状	<32°C Solid,>34°C Liquid
IC50 & Target[1][2]	CPT-1a
体外研究(In Vitro)	Etomoxir binds irreversibly to the catalytic site of CPT-1 inhibiting its activity, but also upregulates fatty acid oxidation enzymes. Etomoxir is developed as an inhibitor of the mitochondrial carnitine palmitoyltransferase-1 (CPT-1) located on the outer mitochondrial membrane. Etomoxir, in the liver can act as peroxisomal proliferator, increasing DNA synthesis and liver growth. Thus, etomoxir, in addition of being a CPT1 inhibitor could be considered as a PPARalpha agonist. Etomoxir is a member of the oxirane carboxylic acid carnitine palmitoyl transferase I inhibitors and has been suggested as a therapeutic agent for the treatment of heart failure. Acute Etomoxir treatment irreversibly inhibits the activity of carnitine palmitoyltransferase I. As a result, fatty acid import into the mitochondria and β-oxidation is reduced, whereas cytosolic fatty acid accumulates and glucose oxidation is elevated. Prolonged incubation (24 h) with Etomoxir produces diverse effects on the expression of several metabolic enzyme. Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究(In Vivo)	Etomoxir is an inhibitor of free fatty acid (FFA) oxidation-related key enzyme CPT1. P53 interacts directly with Bax, which is inhibited by Etomoxir, further confirming the direct interaction of P53 and Bax, and the involvement of FAO-mediated mitochondrial ROS generation in db/db mice. Rats are injected daily with Etomoxir, a specific CPT-I inhibitor, for 8 days at 20 mg/kg of body mass. Etomoxir-treated rats display a 44% reduced cardiac CPT-I activity. The treatment of Lewis rats for 8 days with 20 mg/kg Etomoxir does not alter blood glucose, which is in line with comparable etomoxir-feeding studies. Similarly, Etomoxir feeding does not affect general growth characteristics such as gain in body mass, nor does it affect hindlimb muscle mass. However, heart mass and liver mass are both significantly increased by 11% in Etomoxir-treated rats. Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
运输条件	Room temperature or refrigerated transportation.
储存方式	-20°C, protect from light, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
参考文献	[1]. Rupp H, et al. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002 Nov;27(7):621-36. [Information] [2]. Xu FY, et al. Etomoxir mediates differential metabolic channeling of fatty acid and glycerol precursors into cardiolipin in H9c2 cells. J Lipid Res. 2003 Feb;44(2):415-23. [Information] [3]. Li J, et al. FFA-ROS-P53-mediated mitochondrial apoptosis contributes to reduction of osteoblastogenesis and bone mass in type 2 diabetes mellitus. Sci Rep. 2015 Jul 31;5:12724. [Information] [4]. Luiken JJ, et al. Etomoxir-induced partial carnitine palmitoyltransferase-I (CPT-I) inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates. Biochem J. 2009 Apr 15;419(2):447-55. [Information] [5]. OConnor RS, et al. The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations. Sci Rep. 2018 Apr 19;8(1):6289. [Information]

溶解度数据

体外研究:

DMSO : 100 mg/mL (305.98 mM; ultrasonic and warming and heat to 60°C)

配制储备溶液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	3.0598 mL	15.2989 mL	30.5979 mL
5 mM	0.6120 mL	3.0598 mL	6.1196 mL
10 mM	0.3060 mL	1.5299 mL	3.0598 mL

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，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, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。

体内研究:

建议根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都建议先按照 体外研究 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

建议依照次序添加每种溶剂： 0.5% Methylcellulose/saline water
Solubility: 10 mg/mL (30.60 mM); Suspended solution; Need ultrasonic
2.

建议依照次序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 3.5 mg/mL (10.71 mM); Suspended solution; Need ultrasonic

此方案可获得 3.5 mg/mL (10.71 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 35.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

建议依照次序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 3.5 mg/mL (10.71 mM); Clear solution

此方案可获得 ≥ 3.5 mg/mL (10.71 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 35.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
4.

建议依照次序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: 2.5 mg/mL (7.65 mM); Clear solution; Need ultrasonic

此方案可获得 2.5 mg/mL (7.65 mM) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH?O 中，得到澄清透明的生理盐水溶液

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产品使用指南

Data Sheet

1：一般建议：溶解度为Medlife测试数据，可能与文献描述存在差异。这是由于生产工艺和批次不同产生的正常现象。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。不同批次产品溶解度各有差异，仅做参考，具体以实验方案为准。

2：储存条件：粉末-20°C一般情况可以保存3年，溶于溶剂-80°C一般情况可以保存1年。不同产品及不同批次产品可能存在差异，请细致阅读产品信息，并辅助参考相关文献描述。

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