BMS-201038

BMS-201038 is a MTP inhibitor. Lomitapid is a novel agent for the treatment of homozygous familial hypercholesterolemia. Lomitapide is an orally active inhibitor of microsomal triglyceride transfer protein that is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available for the reduction of LDL-C, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol in adult patients with HoFH.

Product information

CAS Number: 182431-12-5

Molecular Weight: 693.72

Formula: C39H37F6N3O2

Synonym:

Lomitapide free base

AEGR-733

BMS-201038

BMS 201038-01

Lomitapide mesylate

Juxtapid

Lojuxta

AEGR 733

AEGR733

BMS 201038

BMS201038

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

Smiles: O=C(NCC(F)(F)F)C1(CCCCN2CCC(CC2)NC(=O)C2=CC=CC=C2C2C=CC(=CC=2)C(F)(F)F)C2=CC=CC=C2C2=CC=CC=C12

InChiKey: MBBCVAKAJPKAKM-UHFFFAOYSA-N

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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

BMS-201038 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. BMS-201038 undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin.

In Vivo:

The use of BMS-201038 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%. BMS-201038 is associated with significant gastrointestinal adverse effects and increases in hepatic fat levels. The bioavailability of the 50-mg BMS-201038 capsule is 7.1%. The mean half-life of BMS-201038 is 39.7 hours. Single-dose administration of BMS-201038 is shown to reduce serum triglycerides by 35% and 47% at 0.3- and 1-mg/kg doses, respectively. Multiple-dose treatment with BMS-201038 also results in dose dependent decrease in triglycerides (71%–87%), nonesterified fattyacids(33%–40%), and LDL-C(26-29%).

References:

1. Marbach JA, Thapa J, Goldenberg E, Duffy D. Pharmacogenetics in the Development of Lipid Lowering Medications: Lomitapide & Mipomersen in Clinical Practice. Del Med J. 2015 Aug;87(8):238-43. PubMed PMID: 26402926.
2. Roeters van Lennep J, Averna M, Alonso R. Treating homozygous familial hypercholesterolemia in a real-world setting: Experiences with lomitapide. J Clin Lipidol. 2015 Jul-Aug;9(4):607-17. doi: 10.1016/j.jacl.2015.05.001. Epub 2015 May 14. PubMed PMID: 26228681.
3. Patel G, King A, Dutta S, Korb S, Wade JR, Foulds P, Sumeray M. Evaluation of the effects of the weak CYP3A inhibitors atorvastatin and ethinyl estradiol/norgestimate on lomitapide pharmacokinetics in healthy subjects. J Clin Pharmacol. 2015 Jun 26. doi: 10.1002/jcph.581. [Epub ahead of print] PubMed PMID: 26120010.
4. Gouni-Berthold I, Berthold HK. Mipomersen and lomitapide: Two new drugs for the treatment of homozygous familial hypercholesterolemia. Atheroscler Suppl. 2015 May;18:28-34. doi: 10.1016/j.atherosclerosissup.2015.02.005. PubMed PMID: 25936301.
5. Stefanutti C, Blom DJ, Averna MR, Meagher EA, Theron Hd, Marais AD, Hegele RA, Sirtori CR, Shah PK, Gaudet D, Vigna GB, Sachais BS, Di Giacomo S, du Plessis AM, Bloedon LT, Balser J, Rader DJ, Cuchel M; Phase 3 HoFH Lomitapide Study Investigators. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial. Atherosclerosis. 2015 Jun;240(2):408-14. doi: 10.1016/j.atherosclerosis.2015.03.014. Epub 2015 Mar 14. PubMed PMID: 25897792; PubMed Central PMCID: PMC4573555.

Products are for research use only. Not for human use.