lomitapide   Click here for help

GtoPdb Ligand ID: 7439

Synonyms: AEGR-733 | BMS-201038 | Juxtapid® | Lojuxta®
Approved drug
lomitapide is an approved drug (FDA (2012), EMA (2013))
Compound class: Synthetic organic
Comment: Lomitapide is a lipid-lowering agent for the treatment of familial hypercholesterolemia.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: lomitapide

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 14
Topological polar surface area 61.44
Molecular weight 693.28
XLogP 10.09
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=C(c1ccccc1c1ccc(cc1)C(F)(F)F)NC1CCN(CC1)CCCCC1(C(=O)NCC(F)(F)F)c2ccccc2c2c1cccc2
Isomeric SMILES O=C(c1ccccc1c1ccc(cc1)C(F)(F)F)NC1CCN(CC1)CCCCC1(C(=O)NCC(F)(F)F)c2ccccc2c2c1cccc2
InChI 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)
InChI Key MBBCVAKAJPKAKM-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Approved to lower total cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). Clinical formulations contain lomitapide mesylate (PubChem CID 11274333).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Mechanistically lomatipide inhibits microsomal triglyceride transfer protein (MTTP, P55157). MTTP is required for the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces in the endoplasmic reticulum and this activity is required for the synthesis of apolipoprotein B (apo B). Lomatipide-induced reduction of apoB reduces VLDL and chylomicron formation and thus reduces LDL-cholesterol levels. Note that the microsomal triglyceride transfer protein is a heterodimer, composed of MTTP and protein disulfide isomerase (PDI, of which there are many isoforms).
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)