Microsomal triglyceride transfer protein (MTP) is a multifunctional protein, and its deregulation during pathophysiological conditions gives rise to different metabolic conditions[3]. MTP plays an essential role in lipid metabolism, especially in the biogenesis of very low-density lipoproteins and chylomicrons via the transfer of neutral lipids and the assembly of apoB-containing lipoproteins[4]. Lomitapide is a small-molecule, MTP inhibitor, for the treatment of both familial and primary hypercholesterolemia. Oral, once-daily lomitapide will be targeted at patients resistant to HMG-CoA reductase inhibitors (statins) either due to abnormalities in liver function or to discontinuation because of muscle pain[5]. Lomitapide is an orally administered inhibitor of the microsomal triglyceride transfer protein, inhibits the synthesis of chylomicrons and very low-density lipoprotein, thereby reducing plasma levels of low-density lipoprotein cholesterol (LDL-C)[6]. Lomitapide undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin; dose adjustment is recommended when lomitapide is used concurrently with these agents[7]. In the presence of an up-titration regiment and low-fat diet, lomitapide is generally well tolerated and liver fat accumulation stabilizes after the initial increase. Elevation of alanine aminotranferase levels greater than 3 times the upper limit of normal can be managed successfully with temporary dose reduction[8].
Lomitapide mesylate/甲磺酸洛美他派 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Panc-1 cells
3.5 μM, 1.75 μM, 0.875 μM
15 days
Assess the effect of Lomitapide on colony formation of Panc-1 cells, results showed Lomitapide significantly inhibited colony formation in a dose-dependent manner
Cell Death Discov. 2023 Feb 11;9(1):60.
SW1990 cells
2.786–7.293 μM
Evaluate the inhibitory effect of Lomitapide on pancreatic cancer cell lines, results showed Lomitapide significantly inhibited cell proliferation
Cell Death Discov. 2023 Feb 11;9(1):60.
SW480 colorectal cancer cells
0, 5 µM
48 h
To evaluate the effect of Lomitapide on the colony formation of SW480 cells, results showed that Lomitapide significantly inhibited the colony formation of SW480 cells.
Cell Death Dis. 2022 Jul 12;13(7):603.
HT29 colorectal cancer cells
0, 5 µM
48 h
To evaluate the effect of Lomitapide on the colony formation of HT29 cells, results showed that Lomitapide significantly inhibited the colony formation of HT29 cells.
Cell Death Dis. 2022 Jul 12;13(7):603.
HCT116 colorectal cancer cells
0, 1, 2, 5, 10 µM
24 h
To evaluate the effect of Lomitapide on the viability of HCT116 cells, results showed that Lomitapide significantly reduced the viability of HCT116 cells.
Cell Death Dis. 2022 Jul 12;13(7):603.
Neuro-2a cells
0.01, 0.1, and 1 μM
24 h
Lomitapide alleviated cell damage caused by OGD and improved cell viability in a concentration-dependent manner.
CNS Neurosci Ther. 2022 Dec;28(12):2183-2194.
Mouse primary neurons
0.01, 0.1, and 1 μM
24 h
Lomitapide alleviated cell damage caused by OGD and improved cell viability in a concentration-dependent manner.
CNS Neurosci Ther. 2022 Dec;28(12):2183-2194.
Human Umbilical Vein Endothelial Cells (HUVEC)
100 nM
24 h
To dissect the direct effect of lomitapide on endothelial function and integrity, results showed that lomitapide did not reduce the damage in endothelial cells after palmitate treatment.
Obesity (Silver Spring). 2022 Apr;30(4):893-901.
Staphylococcus aureus
12.5–50 μM
24 h
Lomitapide exhibited broad-spectrum antibacterial activity against Gram-positive bacteria, including inhibition of planktonic cell growth and biofilm formation in Staphylococcus aureus.
BMC Microbiol. 2022 Apr 26;22(1):114.
Lomitapide mesylate/甲磺酸洛美他派 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c female nude mice
Mia PaCa-2 xenograft model
Intraperitoneal injection
12 mg/kg, 8 mg/kg, 4 mg/kg
Once daily for 3 weeks
Evaluate the antitumor effect of Lomitapide in vivo, results showed Lomitapide significantly reduced tumor volume and weight, and inhibited tumor cell proliferation
Cell Death Discov. 2023 Feb 11;9(1):60.
Mice
HCT116 and HT29 colorectal cancer xenograft models
Intraperitoneal injection
10, 20, 25, 50 mg/kg
Every 2 days for 10 days
To evaluate the effect of Lomitapide on the growth of HCT116 and HT29 xenograft tumors, results showed that Lomitapide significantly inhibited tumor growth.
Cell Death Dis. 2022 Jul 12;13(7):603.
C57BL/6J mice
Middle cerebral artery occlusion model
Oral
0.5 mg/kg
Once daily for 14 days
Lomitapide significantly increased the survival rate, reduced the neuronal tissue loss, and improved the neurological function.
CNS Neurosci Ther. 2022 Dec;28(12):2183-2194.
Mice
LDLr−/− mice
Oral gavage
1 mg/kg
Once daily for 2 weeks
To investigate the effect of Lomitapide on cardiovascular function in LDLr?/? mice induced by a high-fat diet. Results showed that Lomitapide significantly reduced, blood glucose, and lipid levels, improved endothelial function, and decreased atherosclerotic plaque area.
Antioxidants (Basel). 2023 Jun 16;12(6):1287
Mice
High-fat diet-induced obesity model
Oral gavage
1 mg/kg
Once daily for 2 weeks
To investigate the effect of lomitapide on cardiovascular function in obese mice, results showed that lomitapide treatment attenuated the increase in, improved lipid profile and vascular function, and reduced inflammation, ER stress, and oxidative stress.
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