Lapaquistat acetate

产品说明书

Print
Chemical Structure| 189060-13-7 同义名 : TAK-475
CAS号 : 189060-13-7
货号 : A357554
分子式 : C33H41ClN2O9
纯度 : 98%
分子量 : 645.14
MDL号 : MFCD06407873
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Squalene synthase (SQS) catalyzes the conversion of two farnesyl pyrophosphates to squalene, an important intermediate in between isoprene and valuable triterpenoids[3]. Squalene synthase was up-regulated in CL1-5 cells and in the tumor regions of the lung cancer specimens. Loss of function or knockdown of SQS significantly inhibited invasion/migration and metastasis in cell and animal models and vice versa. High expression of SQS was significantly associated with poor prognosis among patients with lung cancer. Mechanistically, SQS contributed to a lipid-raft-localized enrichment of tumor necrosis factor receptor 1 in a cholesterol-dependent manner, which resulted in the enhancement of nuclear factor-κB activation leading to matrix metallopeptidase 1 up-regulation[4]. Lapaquistat acetate (TAK-475) is a squalene synthase inhibitor, blocking the conversion of farnesyl diphosphate (FPP) to squalene in the cholesterol biosynthesis pathway[5]. Lapaquistat acetate is effective at lowering low-density lipoprotein cholesterol, but it might cause liver damage. Lapaquistat acetate is used for hypercholesterolemia and mevalonate kinase deficiency (MKD) research[6]. Lapaquistat acetate (diet supplemented; 100 or 200 mg/kg; 32 weeks) decreases plasma cholesterol and triglyceride levels. It delays progression of coronary atherosclerosis and changes coronary atheromatous plaques from unstable, macrophage/lipid accumulation-rich, lesions to stable fibromuscular lesions in vivo[7].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00143676 Hypercholesterolemia Phase 3 Completed - -
NCT00286481 Hypercholesterolemia Phase 3 Completed - -
NCT00256178 Hypercholesterolemia Phase 3 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.55mL

0.31mL

0.16mL

7.75mL

1.55mL

0.78mL

15.50mL

3.10mL

1.55mL
参考文献

[1]Stein EA, Bays H, et al. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation. 2011 May 10;123(18):1974-85.

[2]Shiomi M, Yamada S, et al. Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions. Br J Pharmacol. 2008 Jul;154(5):949-57.

[3]Yafeng Song,et al. Production of Squalene in Bacillus subtilis by Squalene Synthase Screening and Metabolic Engineering. J Agric Food Chem. 2020 Apr 15;68(15):4447-4455.

[4]Yi-Fang Yang,et al. Squalene synthase induces tumor necrosis factor receptor 1 enrichment in lipid rafts to promote lung cancer metastasis. Am J Respir Crit Care Med.2014 Sep 15;190(6):675-87.

[5]Stein EA, et al. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation. 2011 May 10;123(18):1974-85.

[6]Marcuzzi A, et al. Repositioning of Tak-475 In Mevalonate Kinase Disease: Translating Theory Into Practice. Curr Med Chem. 2018;25(24):2783-2796.

[7]M Shiomi, et al. Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions. Br J Pharmacol. 2008 Jul;154(5):949-57.