WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 314228
CAS#: 202914-84-9 (mesylate)
Description: Lomitapide 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.
MedKoo Cat#: 314228
Name: Lomitapide mesylate
CAS#: 202914-84-9 (mesylate)
Chemical Formula: C40H41F6N3O5S
Exact Mass:
Molecular Weight: 789.83
Elemental Analysis: C, 60.83; H, 5.23; F, 14.43; N, 5.32; O, 10.13; S, 4.06
Related CAS #: 202914-84-9 (mesylate) 182431-12-5 (free base)
Synonym: AEGR 733; AEGR733; AEGR-733; BMS 201038; BMS-201038; BMS201038; BMS 201038-01. Lomitapide mesylate. Brand name: Juxtapid; Lojuxta.
IUPAC/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 methanesulfonate
InChi Key: QKVKOFVWUHNEBX-UHFFFAOYSA-N
InChi Code: InChI=1S/C39H37F6N3O2.CH4O3S/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;1-5(2,3)4/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49);1H3,(H,2,3,4)
SMILES Code: 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.OS(=O)(C)=O
Appearance: White to off-white Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO.
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Lomitapide mesylate(AEGR-733; BMS-201038) is an inhibitor of microsomal triglyceride-transfer protein (MTP) wtih in vitro IC50 of 8 nM. |
| In vitro activity: | Bayesian statistics was previously used as a tool to virtually screen USFDA approved drugs for predicted β-haematin (synthetic haemozoin) inhibition and in vitro antimalarial activity. Here, the experimental evaluation of nine of the highest ranked drugs, is reported, confirming the accuracy of the model by showing an overall 93% hit rate. Lapatinib, nilotinib, and lomitapide showed the best activity for inhibition of β-haematin formation and parasite growth and were found to inhibit haemozoin formation in the parasite, providing mechanistic insights into their mode of antimalarial action. Furthermore, the SBVS method correctly identified the three most important β-haematin inhibiting drugs identified in the USFDA set using the Bayesian model, namely lapatinib, nilotinib, and lomitapide. Lapatinib, nilotinib, and lomitapide were all found to increase the freely exchangeable haem, and decrease haemozoin in a dose dependent manner confirmed by an unpaired two tailed t-test relative to control, therefore confirming that these drugs inhibit cellular haemozoin formation (Figure 2). Reference: Molecules. 2020 Apr; 25(7): 1571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180468/ |
| In vivo activity: | To evaluate whether the new animal model in which ldlr mutant zebrafish are subjected to short-term (5 days) HCD feeding can be useful for drug screening, the effects of probucol, an antioxidant, and lomitapide, an MTP inhibitor, were tested on vascular lipid accumulation. Both probucol and lomitapide have been shown to exert antioxidant and MTP inhibitor properties, respectively, in zebrafish. As was expected, lomitapide decreased the plasma lipid levels in ldlr mutants, as assessed by ORO staining (Fig. 5A), by blocking their absorption in the intestine. Vascular lipid deposits were not decreased by probucol treatment but were significantly decreased by the treatment with lomitapide (Fig. 5B, C), suggesting that lipid levels, but not lipid oxidation, play a dominant role in early vascular lipid accumulation event in loss-of-function ldlr mutant larvae. Reference: J Lipid Res. 2018 Feb; 59(2): 391–399. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794413/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 126.61 | |
| Ethanol | 100.0 | 126.61 |
The following data is based on the product molecular weight 789.83 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. de Sousa ACC, Maepa K, Combrinck JM, Egan TJ. Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites. Molecules. 2020 Mar 29;25(7):1571. doi: 10.3390/molecules25071571. PMID: 32235391; PMCID: PMC7180468. 2. Liu C, Kim YS, Kim J, Pattison J, Kamaid A, Miller YI. Modeling hypercholesterolemia and vascular lipid accumulation in LDL receptor mutant zebrafish. J Lipid Res. 2018 Feb;59(2):391-399. doi: 10.1194/jlr.D081521. Epub 2017 Nov 29. PMID: 29187523; PMCID: PMC5794413 |
| In vitro protocol: | 1. de Sousa ACC, Maepa K, Combrinck JM, Egan TJ. Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites. Molecules. 2020 Mar 29;25(7):1571. doi: 10.3390/molecules25071571. PMID: 32235391; PMCID: PMC7180468. |
| In vivo protocol: | 1. Liu C, Kim YS, Kim J, Pattison J, Kamaid A, Miller YI. Modeling hypercholesterolemia and vascular lipid accumulation in LDL receptor mutant zebrafish. J Lipid Res. 2018 Feb;59(2):391-399. doi: 10.1194/jlr.D081521. Epub 2017 Nov 29. PMID: 29187523; PMCID: PMC5794413 |
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.
6: Goulooze SC, Cohen AF, Rissmann R. Lomitapide. Br J Clin Pharmacol. 2015 Aug;80(2):179-81. doi: 10.1111/bcp.12612. Epub 2015 Jul 2. PubMed PMID: 25702706; PubMed Central PMCID: PMC4541964.
7: Alonso R, Mata P, Alonso Y Gregorio M, de Andrés R. [Homozygous familial hypercholesterolemia. First case in Spain treated with lomitapide, an inhibitor of the synthesis of lipoproteins with apolipoprotein B]. Med Clin (Barc). 2015 Sep 7;145(5):229-30. doi: 10.1016/j.medcli.2014.11.002. Epub 2014 Dec 24. Spanish. PubMed PMID: 25543225.
8: deGoma EM. Correction to "lomitapide for the management of homozygous familial hypercholesterolemia". Rev Cardiovasc Med. 2014;15(3):281-2. PubMed PMID: 25290735.
9: Catapano AL. Management of homozygous familial hypercholesterolaemia--unmet needs, updated recommendations, and clinical experience with the MTP inhibitor, lomitapide. Concluding comments. Atheroscler Suppl. 2014 Sep;15(2):52. doi: 10.1016/j.atherosclerosissup.2014.07.001. Review. PubMed PMID: 25257077.
10: Cuchel M, Blom DJ, Averna MR. Clinical experience of lomitapide therapy in patients with homozygous familial hypercholesterolaemia. Atheroscler Suppl. 2014 Sep;15(2):33-45. doi: 10.1016/j.atherosclerosissup.2014.07.005. Review. PubMed PMID: 25257075.
11: Sacks FM, Stanesa M, Hegele RA. Progression to hepatitis and fibrosis secondary to lomitapide use--reply. JAMA Intern Med. 2014 Sep;174(9):1522-3. doi: 10.1001/jamainternmed.2014.1528. PubMed PMID: 25178869.
12: Miyares MA. Progression to hepatitis and fibrosis secondary to lomitapide use: selecting the next course of action. JAMA Intern Med. 2014 Sep;174(9):1522. doi: 10.1001/jamainternmed.2014.1538. PubMed PMID: 25178868.
13: deGoma EM. Lomitapide for the management of homozygous familial hypercholesterolemia. Rev Cardiovasc Med. 2014;15(2):109-18. Review. PubMed PMID: 25051128.
14: Davis KA, Miyares MA. Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia. Am J Health Syst Pharm. 2014 Jun 15;71(12):1001-8. doi: 10.2146/ajhp130592. Review. PubMed PMID: 24865757.
15: Tuteja S, Duffy D, Dunbar RL, Movva R, Gadi R, Bloedon LT, Cuchel M. Pharmacokinetic interactions of the microsomal triglyceride transfer protein inhibitor, lomitapide, with drugs commonly used in the management of hypercholesterolemia. Pharmacotherapy. 2014 Mar;34(3):227-39. PubMed PMID: 24734312.
16: Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014 Mar 4;129(9):1022-32. doi: 10.1161/CIRCULATIONAHA.113.001292. Review. PubMed PMID: 24589695.
17: Sacks FM, Stanesa M, Hegele RA. Severe hypertriglyceridemia with pancreatitis: thirteen years' treatment with lomitapide. JAMA Intern Med. 2014 Mar;174(3):443-7. doi: 10.1001/jamainternmed.2013.13309. PubMed PMID: 24366202.
18: Dixon DL, Sisson EM, Butler M, Higbea A, Muoio B, Turner B. Lomitapide and mipomersen: novel lipid-lowering agents for the management of familial hypercholesterolemia. J Cardiovasc Nurs. 2014 Sep-Oct;29(5):E7-E12. doi: 10.1097/JCN.0000000000000104. Review. PubMed PMID: 24231894.
19: Hussar DA, Ahmad A. Vilanterol trifenatate/fluticasone furoate, lomitapide mesylate, and mipomersen sodium. J Am Pharm Assoc (2003). 2013 Nov-Dec;53(6):662-70. doi: 10.1331/JAPhA.2013.13538. PubMed PMID: 24185435.
20: Darpo B, Ferber G, Zhou M, Sumeray M, Sager P. Lomitapide at supratherapeutic plasma levels does not prolong the Qtc interval--results from a TQT study with moxifloxacin and ketoconazole. Ann Noninvasive Electrocardiol. 2013 Nov;18(6):577-89. doi: 10.1111/anec.12103. Epub 2013 Sep 30. PubMed PMID: 24118671.
