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Perhexiline(maleate)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Perhexiline(maleate)图片
包装与价格:
包装价格(元)
1mg电议
5mg电议
10mg电议

产品介绍
Perhexiline (maleate) 是一种具有口服活性的 CPT1 和 CPT2 抑制剂,可降低脂肪酸代谢。

Cell experiment:

The effect of antitumoral drugs on neuroblastoma cell survival is evaluated using the MTT assay. Approximately 24 hours after plating, cells are exposed to Perhexiline maleate (0.01 μM) for 48 hours at 37℃. Cytotoxicity is expressed as the percentage of cells surviving in relation to untreated cells[2].

Animal experiment:

Mice: In protocol a, 21 mice are divided in 4 groups: control vehicle group: DMSO; cisplatin (3 mg/kg/dose) treated group; Perhexiline (1 mg/kg/dose) treated group and; Perhexiline (1 mg/kg/dose) and cisplatin (3 mg/kg/dose) treated group. In protocol b, 20 mice are divided in 4 groups: control vehicle group: DMSO; Perhexiline (3 mg/kg/dose) treated group; cisplatin (5 mg/kg/dose) treated group; Perhexiline (3 mg/kg/dose) and cisplatin (5 mg/kg/dose) treated group[2].

产品描述

Perhexiline maleate, an anti-anginal metabolic modulator, blocks the mitochondrial enzyme carnitine palmitoyltransferase 1 (CPT1) and to a lesser extent CPT2, which triggers causes a shift in myocardial substrate utilization from long chain fatty acids to carbohydrates, leading to the increased glucose and lactate utilization and increased ATP production for the same O2 consumption and consequently improves myocardial efficiency.

CPT1 and CPT2 are mitochondrial enzymes which oxidize long-chain fatty acids in the mitochondria. Additionally, perhexiline maleate is found to suppress the activity of Mammalian target of rapamycin complex 1 (mTORC1) which controls the initiation step of protein synthesis via the phosphorylation of eukaryotic initiation factor 4E-binding proteins and of ribosomal S6 kinases.

In vitro: Perhexiline maleate concentration-dependently and competitively inhibited CPT1 in rat cardiac and hepatic mitochondria, with an IC50 value of 77 and 148 μM, respectively. It was indicated that perhexiline maleate displayed a greater sensitivity of the cardiac than the hepatic enzyme when exhibiting inhibition effect [1]. Perhexiline maleate produced concentration-dependent inhibition of CPT2 activity with an IC50 value of 79 μM [2]. In human breast cancer MCF-7 cells, Perhexiline maleate blocked mTORC1 signaling at 10 μM and elicited autophagy ~7-fold at a concentration of 10 μM [3].

In vivo: Adult mice of Swiss NMRI strain were orally administrated with perhexiline maleate at a dosage of 100 mg/kg body weight/day for 10 weeks. Perhexiline maleate triggered changes in nerve, including a few cytoplasmic inclusions in Schwann and perineurial cells of mice treated with perhexiline maleate. After 11 weeks of administration of the drug, and up to 18 weeks, small abnormal zones were displayed on several muscle fibers, which were formed by tubular aggregates [4].

References:
[1].  Kennedy, J., Unger, S., & Horowitz, J. Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochemical Pharmacology. 1996; 52(2): 273-280.
[2].  Kennedy, J., Kiosoglous, A., Murphy, G., Pelle, M., & Horowitz, J. Effect of Perhexiline and Oxfenicine on Myocardial Function and Metabolism During Low-Flow Ischemia/Reperfusion in the Isolated Rat Heart. Journal of Cardiovascular Pharmacology. 2000; 36(6): 794-801.
[3].  Balgi, A., Fonseca, B., Donohue, E., Tsang, T., Lajoie, P., & Proud, C. et al. Screen for Chemical Modulators of Autophagy Reveals Novel Therapeutic Inhibitors of mTORC1 Signaling. Plos ONE. 2009; 4(9): e7124.
[4].  Fardeau, M., Tomé, F., & Simon, P. Muscle and nerve changes induced by perhexiline maleate in man and mice. Muscle & Nerve. 1979; 2(1): 24-36.