PRD125

PRD125 is an orally active small molecule that functions as a dual inhibitor of Acyl-CoA:cholesterol acyltransferase 2 (ACAT2) and Proprotein convertase subtilisin/kexin type 9 (PCSK9). Originally identified as a selective ACAT2 inhibitor, PRD125 was subsequently found to posttranscriptionally reduce PCSK9 protein levels without altering mRNA expression. In preclinical models, PRD125 administration led to significant reductions in serum LDL-cholesterol and PCSK9 concentrations, alongside improvements in glucose tolerance and insulin sensitivity (HOMA-IR). The compound has demonstrated efficacy in reducing atherosclerosis in mice, positioning it as a potential multifunctional therapeutic for cardiometabolic diseases. It was developed by researchers at the Karolinska Institutet and Kitasato University.