AEGR-733(Lomitapide)

Cas No.:	182431-12-5
Chemical Name:	N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide
Synonyms:	N-(2,2,2-Trifluoroethyl)-9-(4-[4-[4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamido]piperidin-1-yl]butyl)-9H-fluorene-9-carboxamide;AEGR 733;N-(2,2,2-trifluoroethyl)-9-(4-(4-(4'-(trifluoromethyl)biphenyl-2-ylcarboxamido)piperidin-1-yl)butyl)-9H-fluorene-9-carboxamide;N-(2,2,2-trifluoroethyl)-9-[4-[4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]piperidin-1-yl]butyl]fluorene-9-carboxamide;AEGR-733;BMS201038;BMS-201038;N-(2,2,2-Trifluoroethyl)-9-[4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]2-yl]carbonyl]amino]-1-piperidinyl]butyl]9H-fluoren-9-carboxamde;N-(2,2,2-Trifluoroethyl)-9-[4-[4-[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-ylcarboxamido]piperidin-1-yl]butyl]-9H-fluorene-9-carboxamide;LoMitapide;BMS 201238;BMS 201038-01;AEGR-733(Lomitapide)free base;N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide
SMILES:	O=C(C1(CCCCN2CCC(NC(C3=CC=CC=C3C4=CC=C(C(F)(F)F)C=C4)=O)CC2)C5=C(C6=C1C=CC=C6)C=CC=C5)NCC(F)(F)F
Formula:	C39H37N3O2F6
M.Wt:	693.72038
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Lomitapide (AEGR-733; BMS-201038) is a potent inhibitor of microsomal triglyceride-transfer protein (MTP) with an IC50 of 8 nM in vitro.
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].
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].