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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
Structure of LOMITAPIDE

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)

HIDE SMILES / InChI

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

Description

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
8.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
JUXTAPID
PubMed

PubMed

TitleDatePubMed
Gateways to clinical trials.
2009 Jun
Lomitapide, a microsomal triglyceride transfer protein inhibitor for the treatment of hypercholesterolemia.
2010 Feb
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
In in vitro experiments using unilamellar vesicles, lomitapide inhibited rat, hamster, and human MTP with an inhibitory concentration of 50% (IC50) of 5 to 7 nmol/L. In vitro studies demonstrated a reduction in apoB secretion by hepatocytes on treatment with lomitapide
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:49:25 UTC 2019
Edited
by admin
on Mon Oct 21 20:49:25 UTC 2019
Record UNII
82KUB0583F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOMITAPIDE
DASH   INN   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
LOMITAPIDE [WHO-DD]
Common Name English
AEGR-733
Code English
JUXTAPID
Brand Name English
LOMITAPIDE [MI]
Common Name English
9H-FLUORENE-9-CARBOXAMIDE, N-(2,2,2-TRIFLUOROETHYL)-9-(4-(4-(((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)CARBONYL)AMINO)-1-PIPERIDINYL)BUTYL)-
Systematic Name English
LOMITAPIDE [USAN]
Common Name English
N-(2,2,2-TRIFLUOROETHYL)-9-(4-(4-(((4'-(TRIFLUOROMETHYL)BIPHENYL-2-YL)CARBONYL)AMINO)PIPERIDIN-1-YL)BUTYL)-9H-FLUORENE-9-CARBOXAMIDE
Systematic Name English
LOMITAPIDE [INN]
Common Name English
BMS-201038-01
Code English
LOMITAPIDE [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29703
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
NDF-RT N0000186779
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
FDA ORPHAN DRUG 245907
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
EU-Orphan Drug EU/3/10/823
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
WHO-VATC QC10AX12
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
WHO-ATC C10AX12
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
FDA ORPHAN DRUG 332110
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
Code System Code Type Description
WIKIPEDIA
LOMITAPIDE
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
NDF-RT
N0000185503
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY P-Glycoprotein Inhibitors [MoA]
INN
9120
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
EVMPD
SUB34920
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
RXCUI
1364479
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY RxNorm
IUPHAR
7439
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
MERCK INDEX
M11671
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
HSDB
182431-12-5
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
NDF-RT
N0000182141
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
PUBCHEM
9853053
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
ChEMBL
CHEMBL354541
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
DRUG BANK
DB08827
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
NDF-RT
N0000186778
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY Microsomal Triglyceride Transfer Protein Inhibitors [MoA]
EPA CompTox
182431-12-5
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
NCI_THESAURUS
C83891
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
LactMed
182431-12-5
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
CAS
182431-12-5
Created by admin on Mon Oct 21 20:49:26 UTC 2019 , Edited by admin on Mon Oct 21 20:49:26 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> NON-INHIBITOR
TARGET -> INHIBITOR
In the small unilamellar vesicle (SUV) assay, IC50 values for isolated human MTP 5 nM.
IC50
METABOLIC ENZYME -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
Lomitapide is a weak in vivo CYP3A inhibitor.
WEAK
BINDER->LIGAND
BINDING
TRANSPORTER -> NON-SUBSTRATE
EXCRETED UNCHANGED
FECAL
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
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
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
METABOLITE -> PARENT
MINOR
FECAL; URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
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
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
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
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE

Volume of Distribution PHARMACOKINETIC SINGLE DOSE

ORAL ADMINISTRATION