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.
Click here for help
IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: lomitapide

2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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)
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