WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 319516
CAS#: 182431-12-5 (free base)
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#: 319516
Name: Lomitapide free base
CAS#: 182431-12-5 (free base)
Chemical Formula: C39H37F6N3O2
Exact Mass: 693.279
Molecular Weight: 693.7344
Elemental Analysis: C, 67.52; H, 5.38; F, 16.43; N, 6.06; O, 4.61
Related CAS #: 202914-84-9 (mesylate) 182431-12-5 (free base)
Synonym: Lomitapide free base, 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
InChi Key: MBBCVAKAJPKAKM-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NCC(F)(F)F)C1(C2=C(C=CC=C2)C3=C1C=CC=C3)CCCCN4CCC(CC4)NC(C5=CC=CC=C5C6=CC=C(C=C6)C(F)(F)F)=O
Appearance: 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, not in water
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 (AEGR-733; BMS-201038) is a potent inhibitor of microsomal triglyceride-transfer protein (MTP) with an IC50 of 8 nM in vitro. |
| In vitro activity: | The study results showed that lomitapide directly inhibits mTORC1 in vitro and induces autophagy-dependent cancer cell death by decreasing mTOR signaling, thereby inhibiting the downstream events associated with increased LC3 conversion in various cancer cells (e.g., HCT116 colorectal cancer cells) and tumor xenografts. Reference: Cell Death Dis. 2022 Jul 12;13(7):603. https://pubmed.ncbi.nlm.nih.gov/35831271/ |
| In vivo activity: | The in vivo activity of BMS-201038, a potent inhibitor of MTP, was evaluated in a model of hypertriglyceridemia induced by Triton WR1339 and corn oil in Zucker fatty rats. Triglyceride secretion rate was significantly reduced by a single dose of BMS-201038 by 35% at 0.3 mg/kg and 47% at 1 mg/kg, respectively. Reference: Clin Exp Pharmacol Physiol. 2011 May;38(5):338-44. https://pubmed.ncbi.nlm.nih.gov/21401695/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 68.33 | 98.5 | |
| Ethanol | 10.0 | 14.42 |
The following data is based on the product molecular weight 693.7344 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. Lee B, Park SJ, Lee S, Lee J, Lee E, Yoo ES, Chung WS, Sohn JW, Oh BC, Kim S. Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR. Cell Death Dis. 2022 Jul 12;13(7):603. doi: 10.1038/s41419-022-05039-6. PMID: 35831271; PMCID: PMC9279289. 2. Zhang Y, Zhang Y, Chen C, Cheng H, Deng X, Li D, Bai B, Yu Z, Deng Q, Guo J, Wen Z. Antibacterial activities and action mode of anti-hyperlipidemic lomitapide against Staphylococcus aureus. BMC Microbiol. 2022 Apr 26;22(1):114. doi: 10.1186/s12866-022-02535-9. PMID: 35473561; PMCID: PMC9040290. 3. Zheng Y, Hu Y, Han Z, Yan F, Zhang S, Yang Z, Zhao F, Li L, Fan J, Wang R, Luo Y. Lomitapide ameliorates middle cerebral artery occlusion-induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration. CNS Neurosci Ther. 2022 Dec;28(12):2183-2194. doi: 10.1111/cns.13961. Epub 2022 Sep 2. PMID: 36052650; PMCID: PMC9627359. 4. Dhote V, Joharapurkar A, Kshirsagar S, Dhanesha N, Patel V, Patel A, Raval S, Jain M. Inhibition of microsomal triglyceride transfer protein improves insulin sensitivity and reduces atherogenic risk in Zucker fatty rats. Clin Exp Pharmacol Physiol. 2011 May;38(5):338-44. doi: 10.1111/j.1440-1681.2011.05513.x. PMID: 21401695. |
| In vitro protocol: | 1. Lee B, Park SJ, Lee S, Lee J, Lee E, Yoo ES, Chung WS, Sohn JW, Oh BC, Kim S. Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR. Cell Death Dis. 2022 Jul 12;13(7):603. doi: 10.1038/s41419-022-05039-6. PMID: 35831271; PMCID: PMC9279289. 2. Zhang Y, Zhang Y, Chen C, Cheng H, Deng X, Li D, Bai B, Yu Z, Deng Q, Guo J, Wen Z. Antibacterial activities and action mode of anti-hyperlipidemic lomitapide against Staphylococcus aureus. BMC Microbiol. 2022 Apr 26;22(1):114. doi: 10.1186/s12866-022-02535-9. PMID: 35473561; PMCID: PMC9040290. |
| In vivo protocol: | 1. Zheng Y, Hu Y, Han Z, Yan F, Zhang S, Yang Z, Zhao F, Li L, Fan J, Wang R, Luo Y. Lomitapide ameliorates middle cerebral artery occlusion-induced cerebral ischemia/reperfusion injury by promoting neuronal autophagy and inhibiting microglial migration. CNS Neurosci Ther. 2022 Dec;28(12):2183-2194. doi: 10.1111/cns.13961. Epub 2022 Sep 2. PMID: 36052650; PMCID: PMC9627359. 2. Dhote V, Joharapurkar A, Kshirsagar S, Dhanesha N, Patel V, Patel A, Raval S, Jain M. Inhibition of microsomal triglyceride transfer protein improves insulin sensitivity and reduces atherogenic risk in Zucker fatty rats. Clin Exp Pharmacol Physiol. 2011 May;38(5):338-44. doi: 10.1111/j.1440-1681.2011.05513.x. PMID: 21401695. |
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.
