Details
Stereochemistry | ACHIRAL |
Molecular Formula | C39H37F6N3O2 |
Molecular Weight | 693.7204 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
FC(F)(F)CNC(=O)C4(CCCCN1CCC(CC1)NC(=O)C2=C(C=CC=C2)C3=CC=C(C=C3)C(F)(F)F)C5=CC=CC=C5C6=C4C=CC=C6
InChI
InChIKey=MBBCVAKAJPKAKM-UHFFFAOYSA-N
InChI=1S/C39H37F6N3O2/c40-38(41,42)25-46-36(50)37(33-13-5-3-10-30(33)31-11-4-6-14-34(31)37)21-7-8-22-48-23-19-28(20-24-48)47-35(49)32-12-2-1-9-29(32)26-15-17-27(18-16-26)39(43,44)45/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49)
Molecular Formula | C39H37F6N3O2 |
Molecular Weight | 693.7204 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Lomitapide (INN, marketed as Juxtapid in the US and as Lojuxta in the EU) is a drug for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals. It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate. The US Food and Drug Administration (FDA) approved lomitapide on 21 December 2012, as an orphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). On 31 May 2013 the European Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion with a unanimous vote recommending a marketing authorization for lomitapide. On 31 July 2013 the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adult patients with HoFH. UXTAPID directly binds and inhibits microsomal triglyceride transfer protein (MTP), which resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B containing lipoproteins in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and VLDL. The inhibition of the synthesis of VLDL leads to reduced levels of plasma LDL-C.
Originator
Approval Year
PubMed
Title | Date | PubMed |
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Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. | 2007 Jan 11 |
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Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. | 2013 Jan 5 |
Sample Use Guides
Initiate treatment at 5 mg once daily. Titrate dose based on acceptable safety/tolerability: increase to 10 mg daily after at least 2 weeks; and then, at a minimum of 4-week intervals, to 20 mg, 40 mg, and up to the maximum recommended dose of 60 mg daily. Take once daily, whole, with water and without food, at least 2 hours after evening meal.
Route of Administration:
Oral
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Oct 21 20:49:25 UTC 2019
by
admin
on
Mon Oct 21 20:49:25 UTC 2019
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Record UNII |
82KUB0583F
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Record Status |
Validated (UNII)
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Record Version |
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Official Name | English | ||
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Common Name | English | ||
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Code | English | ||
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Brand Name | English | ||
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Common Name | English | ||
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Systematic Name | English | ||
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Systematic Name | English | ||
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Code | English | ||
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Common Name | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29703
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NDF-RT |
N0000186779
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FDA ORPHAN DRUG |
245907
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EU-Orphan Drug |
EU/3/10/823
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WHO-VATC |
QC10AX12
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WHO-ATC |
C10AX12
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FDA ORPHAN DRUG |
332110
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Code System | Code | Type | Description | ||
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LOMITAPIDE
Created by
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PRIMARY | |||
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N0000185503
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PRIMARY | P-Glycoprotein Inhibitors [MoA] | ||
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9120
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PRIMARY | |||
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SUB34920
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PRIMARY | |||
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1364479
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PRIMARY | RxNorm | ||
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7439
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PRIMARY | |||
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M11671
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PRIMARY | |||
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182431-12-5
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PRIMARY | |||
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N0000182141
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PRIMARY | Cytochrome P450 3A4 Inhibitors [MoA] | ||
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9853053
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PRIMARY | |||
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CHEMBL354541
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PRIMARY | |||
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DB08827
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PRIMARY | |||
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N0000186778
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PRIMARY | Microsomal Triglyceride Transfer Protein Inhibitors [MoA] | ||
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182431-12-5
Created by
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PRIMARY | |||
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C83891
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PRIMARY | |||
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182431-12-5
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PRIMARY | |||
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182431-12-5
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PRIMARY |
Related Record | Type | Details | ||
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TRANSPORTER -> NON-INHIBITOR | |||
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TARGET -> INHIBITOR |
In the small unilamellar vesicle (SUV) assay, IC50 values for isolated human MTP 5 nM.
IC50
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> INHIBITOR |
Lomitapide is a weak in vivo CYP3A inhibitor.
WEAK
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BINDER->LIGAND |
BINDING
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TRANSPORTER -> NON-SUBSTRATE | |||
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EXCRETED UNCHANGED |
FECAL
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
In plasma, M1 was the prominent metabolite that accounted for 5.75% of the total radioactivity in 0 €“ 24 hours plasma samples. In urine, M1 was the prominent metabolite that accounted for 4.69% of the dose in the 0 €“96 hours urine samples. In feces, M1 was the minor metabolite that accounted for 0.49%of the dose in the 0 €“ 96 hours feces.
FECAL; PLASMA; URINE
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METABOLITE -> PARENT |
In plasma, M10+M18 accounted for 9.67% (combined) of the total radioactivity in 0 €“ 24 hours plasma samples. In urine, M18 was the prominent metabolite, which accounted for 3.77% of the dose in the 0 €“ 96 hours urine samples.
PLASMA; URINE
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METABOLITE -> PARENT |
MINOR
FECAL; URINE
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
In plasma, M10+M18 accounted for 9.67% (combined) of the total radioactivity in 0 €“ 24 hours plasma samples. In urine, M10 was the minor metabolite, which accounted for 0.33% of the dose in the 0 €“ 96 hours urine samples.
PLASMA; URINE
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METABOLITE -> PARENT |
In plasma, M5 was the prominent metabolite that accounted for 4.26% of the total radioactivity in 0 €“ 24 hours plasma samples. In urine, M5 was the prominent metabolite that accounted for 3.47% of the dose in the 0 €“96 hours urine samples. In feces, M5 was the minor metabolite that accounted for 0.78% of the dose in the 0 €“ 96 hours feces.
FECAL; PLASMA; URINE
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METABOLITE -> PARENT |
In plasma, M3 was the major metabolite that accounted for 17.3% of the plasma radioactivity. In urine, M3 was the minor metabolite that accounted for 0.34% of the dose in the 0 €“96 hours urine samples. In feces, M3 was the minor metabolite that accounted for 1.33 % of the dose in the 0 €“ 96 hours feces.
FECAL; PLASMA; URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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SINGLE DOSE |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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Volume of Distribution | PHARMACOKINETIC |
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SINGLE DOSE |
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