"目录号: HY-14667
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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。
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相关产品
SBE-β-CD-MPTP hydrochloride-Cyclosporin A-Etomoxir-Auranofin-GKT137831-Ceruletide-Acetylcysteine-JC-1-BPTES-Brassinolide-FCCP-IPTG-MTT-RSL3 1S,3R--
生物活性
Description
Lomitapide (AEGR-733; BMS-201038) is a potent inhibitor of microsomal triglyceride-transfer protein (MTP) with anIC50of 8 nMin vitro.
IC50& Target
IC50: 8 nM (MTP)[1]
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 and simvastatin[2].
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].
Clinical Trial
NCT00730236
Aegerion Pharmaceuticals, Inc.-FDA Office of Orphan Products Development
Homozygous Familial Hypercholesterolemia
December 2007
Phase 3
NCT00690443
Aegerion Pharmaceuticals, Inc.
Hypercholesterolemia
May 2008
Phase 2
NCT00405067
Aegerion Pharmaceuticals, Inc.
Hypercholesterolemia
May 2006
Phase 2
NCT00559962
Aegerion Pharmaceuticals, Inc.
Hyperlipidemia
October 2007
Phase 2
NCT00474240
Aegerion Pharmaceuticals, Inc.
Hypercholesterolemia
April 2007
Phase 2
NCT00730236
Aegerion Pharmaceuticals, Inc.-FDA Office of Orphan Products Development
Homozygous Familial Hypercholesterolemia
December 2007
Phase 3
NCT00690443
Aegerion Pharmaceuticals, Inc.
Hypercholesterolemia
May 2008
Phase 2
NCT00405067
Aegerion Pharmaceuticals, Inc.
Hypercholesterolemia
May 2006
Phase 2
NCT00559962
Aegerion Pharmaceuticals, Inc.
Hyperlipidemia
October 2007
Phase 2
NCT00474240
Aegerion Pharmaceuticals, Inc.
Hypercholesterolemia
April 2007
Phase 2
NCT02080455
Aegerion Pharmaceuticals, Inc.
Effect of Atorvastatin on the Pharmacokinetics of Lomitapide
February 2014
Phase 1
NCT02173158
Aegerion Pharmaceuticals, Inc.
Familial Hypercholesterolemia - Homozygous
April 2014
Phase 3
NCT02044419
Aegerion Pharmaceuticals, Inc.
Healthy
October 2013
Phase 1
NCT02135705
Aegerion Pharmaceuticals, Inc.
Homozygous Familial Hypercholesterolemia
March 2014
NCT00943306
Aegerion Pharmaceuticals, Inc.
Familial Hypercholesterolemia
September 2009
Phase 3
NCT02080468
Aegerion Pharmaceuticals, Inc.
Healthy
February 2014
Phase 1
NCT01915771
Aegerion Pharmaceuticals, Inc.
Intra-subject Variability of Pharmacokinetics
August 2013
Phase 1
NCT02765841
Aegerion Pharmaceuticals, Inc.
Homozygous Familial Hypercholesterolemia
May 2016
Phase 3
NCT02399839
Aegerion Pharmaceuticals, Inc.
Pregnancy
October 2014
NCT02399852
Aegerion Pharmaceuticals, Inc.
Homozygous Familial Hypercholesterolemia
April 2015
NCT01760187
Aegerion Pharmaceuticals, Inc.-Richmond Pharmacology Limited
Healthy Volunteer
November 2012
Phase 1
NCT01556906
Aegerion Pharmaceuticals, Inc.-University of Pennsylvania-Doris Duke Charitable Foundation
Homozygous Familial Hypercholesterolemia
June 2003
Phase 2
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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.