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TL;DR
This study used virtual screening and molecular dynamics to identify potential inhibitors of the cholesterol-synthesizing enzyme DHCR24, with irbesartan as a key candidate.
Molecules · 8 authors, 2 centres
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This study used virtual screening and molecular dynamics to identify potential inhibitors of the cholesterol-synthesizing enzyme DHCR24, with irbesartan as a key candidate.
The study aimed to find new cholesterol-lowering drugs by targeting the enzyme DHCR24. Using computational screening of the DrugBank database, four drug candidates (irbesartan, risperidone, tolvaptan, and conivaptan) were identified. Testing in HepG2 cells and a high-fat-diet mouse model showed all four candidates lowered cholesterol and improved liver fat vacuolation. Irbesartan was the most effective, with its mechanism further investigated. An immune complex assay confirmed irbesartan directly inhibits DHCR24 activity with an IC50 value of 602 nM. The study concludes that inhibiting DHCR24 is a potential strategy for new cholesterol-lowering drugs and suggests irbesartan could be repurposed for patients with both hypertension and hyperlipidemia. Limitations include the focus on cell and animal models without human trials, and the need for further mechanistic studies.