We have successfully identified a number of novel MTP inhibitors with single digit nanomolar potency. Analogues 10aq and 10dq demonstrated in vivo efficacy in a murine gut retention assay.
Dyslipidemia is a key risk factor for cardiovascular diseases, and current treatments primarily aim to lower LDL cholesterol levels to prevent conditions like atherosclerosis and myocardial infarction.
Homozygous Familial Hypercholesterolemia (HoFH) results from mutations in the LDL receptor, leading to very high LDL cholesterol levels, which often do not respond well to standard statin therapy.
Lomitapide, a microsomal triglyceride transfer protein inhibitor, has been approved for HoFH treatment; it effectively lowers LDL-C levels without affecting the LDL receptor and has been shown to reduce LDL-C by more than 50% in resistant cases.
Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder that causes extremely high LDL cholesterol levels, leading to heart disease at an early age; lomitapide is a medication designed to lower these cholesterol levels in affected adults and is being tested for safety and efficacy in children.
The APH-19 study involved 43 pediatric patients aged 5-17 years on existing cholesterol treatments; they received varying doses of lomitapide over a 24-week period to measure its effect on LDL cholesterol levels and other lipid parameters.
Results indicated a significant decrease in LDL cholesterol by 53.5% after 24 weeks of treatment, suggesting lomitapide may be effective for managing cholesterol
Cardiovascular Division, Department of Medicine, Lillehei Heart Institute (N.T.V., S.Z.P., R.T.M., L.M.H., J.B.M., M.K., B.K., M.L.B., K.W.P.), University of Minnesota, Minneapolis, MN.
Background: Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that promote ferroptosis.
Background: Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors.
