Lomitapide 是一种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。

Lomitapide is a small molecule inhibitor of microsomal triglyceride transfer protein (MTP), an enzyme located in the lumen of the endoplasmic reticulum responsible for absorbing dietary lipids and transferring triglycerides onto apolipoprotein B (apo-B) in the assembly of very-low-density lipoprotein.

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 through cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin[2].

The use of lomitapide alone or in combination with other lipid-lowering modalities reduces plasma concentrations of low density lipoprotein cholesterol (LDL-C) by an average 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].

182431-12-5

C39H37F6N3O2

693.734

AEGR-733;洛美他派;BMS-201038

DMSO:93 mg/mL (134.3 mM)
H2O:<1 mgml
Ethanol:93 mg/mL (134.3 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years