Lomitapide

An MTTP inhibitor

此产品仅用于科学研究，我们不为任何个人用途提供产品和服务

库存: 现货

可选规格

包装

价格

促销价

数量
5mg

￥450.00

360.00

- +
25mg

￥1775.00

1420.00

- +
100mg

￥4950.00

3960.00

- +

已选 0 种 0 瓶

金额: ￥0.00

首页收藏

Background

Lomitapide (AEGR-733, BMS-201038) is an oral inhibitor of microsomal triglyceride transfer protein [1].

Microsomal triglyceride transfer protein (MTP) plays an important role in lipoprotein assembly. The mutation of MTP can cause abetalipoproteinemia.

Lomitapide is a MTP inhibitor and used for the treatment of homozygous familial hypercholesterolemia. In patients with familial hypercholesterolemia, lomitapide reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% both as monotherapy and in combination with prescribed lipid-lowering therapies [1]. Lomitapide bound to and inhibited MTP within the lumen of the endoplasmic reticulum and inhibited the synthesis of VLDL and chylomicrons, resulting in the reduction of circulating LDL-C concentrations. In human, lomitapide (50 mg) reduced apo B, LDL-C and total cholesterol concentrations in a dose dependent way. However, lomitapide caused significant gastrointestinal (GI) disturbances at the concentration of 100 mg [2].

参考文献:
[1].? Rizzo M. Lomitapide, a microsomal triglyceride transfer protein inhibitor for the treatment of hypercholesterolemia. IDrugs, 2010, 13(2): 103-111.
[2].? Davis KA, Miyares MA. Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia. Am J Health Syst Pharm, 2014, 71(12): 1001-1008.

Protocol

Animal experiment:

Rats: BMS-201038 is formulated in 0.1% hydroxyl ethyl cellulose and 0.5% Tween 80 in deionized water. Rats in the control group are administered vehicle (2 mL/kg) p.o. Fasted rats are administered 0.3 and 1 mg/kg, p.o., BMS-201038, followed 1 h later by 250 mg/kg, i.v., Triton WR1339. Blood samples are obtained from rats up to 240 min after Triton WR1339 injection to estimate serum triglyceride concentrations. For evaluation of post-prandial lipaemia, fasted rats are administered 0.3 and 1 mg/kg, p.o., BMS-201038, followed 1 h later by a corn oil bolus (6 mL/kg) by oral gavage. Blood samples are again collected up to 1440 min after corn oil administration for the estimation of serum triglyceride concentrations[3].

参考文献:

[1]. Sulsky R, et al. 5-Carboxamido-1,3,2-dioxaphosphorinanes, potent inhibitors of MTP. Bioorg Med Chem Lett. 2004 Oct 18;14(20):5067-70.
[2]. Davis KA. et al. Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia. Am J Health Syst Pharm. 2014 Jun 15;71(12):1001-8.
[3]. Dhote V, et al. Inhibition of microsomal triglyceride transfer protein improves insulin sensitivity and reduces atherogenic risk in Zucker fatty rats. Clin Exp Pharmacol Physiol. 2011 May;38(5):338-44.