| Description | Lomitapide (AEGR-733) 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. |
| 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 through cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin[2]. |
| In vivo | 单独使用Lomitapide 或与其他降脂药物联合使用，可使血浆中低密度脂蛋白胆固醇（LDL-C）的浓度平均降低 50%以上。Lomitapide 与明显的胃肠道不良反应和肝脏脂肪水平升高有关。50 毫克Lomitapide 胶囊的生物利用度为 7.1%。Lomitapide 的平均半衰期为 39.7 小时[2]。单剂量服用Lomitapide ，0.3 毫克/千克和 1 毫克/千克的剂量分别可使血清甘油三酯降低 35% 和 47%。Lomitapide 多剂量治疗也会导致甘油三酯（71%-87%）、非酯化脂肪酸（33%-40%）和低密度脂蛋白胆固醇（26%-29%）的剂量依赖性下降[3]。 |
| Target activity | MTP:8 nM |
| Synonyms | AEGR-733, 洛美他派, BMS-201038 |
| molecular weight | 693.72 |
| Molecular formula | C39H37F6N3O2 |
| CAS | 182431-12-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 93 mg/mL (134.3 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: 93 mg/mL (134.3 mM) |
| References | 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. |