Lomitapide (AEGR-733; BMS-2010

Lomitapide  (Synonyms: 洛美他派; AEGR-733; BMS-201038)

Lomitapide (AEGR-733; BMS-201038)是高效的微粒体甘油三酯转移蛋白(MTP)抑制剂， 体内试验的IC₅₀值为8 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
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生物活性    
Lomitapide (AEGR-733; BMS-201038) is a potent inhibitor of microsomal triglyceride-transfer protein (MTP) with an IC50 of 8 nM in vitro.

IC50 & Target    
IC50: 8 nM (MTP)[1]

体外研究(In Vitro)    
Lomitapide is an oral microsomal triglyceride transfer protein (MTP) inhibitor indicated for the treatment of patients with HoFH, a rare form of hypercholesterolemia that can lead to premature atherosclerotic disease. Lomitapide undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including Atorvastatin (HY-B0589) and Simvastatin (HY-17502)[2].

体内研究(In Vivo)    
The use of lomitapide alone or in combination with other lipid-lowering modalities reduces plasma concentrations of low density lipoprotein cholesterol (LDL-C) by a mean of more than 50%. Lomitapide is associated with significant gastrointestinal adverse effects and increases in hepatic fat levels. The bioavailability of the 50-mg lomitapide capsule is 7.1%. The mean half-life of lomitapide is 39.7 hours[2]. Single-dose administration of lomitapide is shown to reduce serum triglycerides by 35% and 47% at 0.3- and 1-mg/kg doses, respectively. Multiple-dose treatment with lomitapide also results in dose dependent decrease in triglycerides (71%–87%), nonesterified fattyacids(33%–40%), and LDL-C(26-29%)[3].

分子量    
693.72

性状    
Solid

Formula    
C39H37F6N3O2

CAS 号    
182431-12-5

中文名称    
洛美他派

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : ≥ 100 mg/mL (144.15 mM)

* "≥" means soluble, but saturation unknown.

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    1.4415 mL    7.2075 mL    14.4150 mL
5 mM    0.2883 mL    1.4415 mL    2.8830 mL
10 mM    0.1442 mL    0.7208 mL    1.4415 mL
*
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, 6 months; -20°C, 1 month。-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。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 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.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.5 mg/mL (3.60 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: 2.5 mg/mL (3.60 mM); Suspended solution; Need ultrasonic

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.5 mg/mL (3.60 mM); Clear solution
 

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. [Content Brief] [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.  [Content Brief] [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.  [Content Brief]