Background: Ezetimibe is used to treat cardiovascular disease as it blocks the sterol transporter Niemann-Pick C1-Like 1 (NPC1CL1) protein. However, recent evidence indicates that Ezetimibe inhibits several cancers indirectly by reducing circulating cholesterol or via specific signalling pathways.
Methods And Results: Our in silico studies indicate that Ezetimibe binds to the Tp53 binding domain in Mdm2, forming a more thermodynamically stable complex than nutlin3a. Furthermore, a docking study of the newly developed inhibitors-RG7388 and RG7112-was conducted. This further showed lower binding energies of -6.337 kcal/mol and -6.222 kcal/mol, respectively, when compared to the -7.919 kcal/mol exhibited by Ezetimibe. We show that Ezetimibe inhibits the growth of several cancer cell lines at concentrations that are not toxic to a normal cell line.
Conclusions: Thus, Ezetimibe is probably active against cancers that overexpress Mdm2. Moreover, inhibitors of RBBP6 may be combined with Ezetimibe for effective anticancer activity. Due to poor oral bioavailability, Ezetimibe must be administered parenterally for cancer treatment.
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http://dx.doi.org/10.3390/biomedicines13010195 | DOI Listing |
Cancer Lett
January 2025
Advanced Medical Research Institute, Qilu College of Medicine, Shandong University, Jinan, 250012, China. Electronic address:
Dysregulated lipid metabolism is linked to tumor progression. In this study, we identified Niemann-Pick C1-like 1 (NPC1L1) as a downstream effector of PKM2. In breast cancer cells, PKM2 knockout (KO) enhanced NPC1L1 expression while downregulating peroxisome proliferator-activated receptor α (PPARα) signaling pathway.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department of Medicine, Division of Nephrology, Northwell Health, Staten Island University Hospital, Staten Island, NY 10305, USA.
: Lipid disorders are very prevalent in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), leading to heightened cardiovascular risk. This review examines the effectiveness of lipid-lowering agents in these populations and explores gaps in the current research. The goal of this review is to assess the efficacy of lipid-lowering therapies in CKD and ESRD patients and identify future research needs.
View Article and Find Full Text PDFJ Clin Med
January 2025
Cardiovascular Department, Fondazione Poliambulanza, 25124 Brescia, Italy.
This study assessed the proportion of secondary cardiovascular prevention patients who achieved low-density lipoprotein (LDL) cholesterol targets as per the 2019 ESC/EAS Dyslipidemia Guidelines. We also evaluated whether lipid-lowering therapies (LLTs) were adjusted in patients not meeting targets and analyzed the likelihood of these modifications achieving recommended levels. A multicenter, cross-sectional observational study retrospectively reviewed medical records of 1909 outpatients in 9 Italian cardiac rehabilitation/secondary prevention clinics from January 2023 to June 2024.
View Article and Find Full Text PDFJ Clin Med
January 2025
Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam.
: Sitosterolemia is a rare autosomal recessive disorder characterized by diverse clinical manifestations ranging from asymptomatic cases to the development of xanthomas, hypercholesterolemia, premature atherosclerosis, or even sudden death during childhood. It results from homozygous or compound heterozygous pathogenic variants in the or genes. Prompt detection and intervention are essential to managing this condition and preventing severe outcomes.
View Article and Find Full Text PDFBiomedicines
January 2025
Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Cnr. Pioneer and Christiaan de Wet Roads, B2-010 Calabash Building, Florida, Johannesburg 1710, South Africa.
Background: Ezetimibe is used to treat cardiovascular disease as it blocks the sterol transporter Niemann-Pick C1-Like 1 (NPC1CL1) protein. However, recent evidence indicates that Ezetimibe inhibits several cancers indirectly by reducing circulating cholesterol or via specific signalling pathways.
Methods And Results: Our in silico studies indicate that Ezetimibe binds to the Tp53 binding domain in Mdm2, forming a more thermodynamically stable complex than nutlin3a.
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