Anacetrapib
Antisense CETP inhibition, unlike anacetrapib, boosts macrophage reverse cholesterol transport in CETP-transgenic mice (J Lipid Res 2013)
Original title: Antisense oligonucleotide inhibition of cholesteryl ester transfer protein enhances RCT in hyperlipidemic, CETP transgenic, LDLr-/- mice
This study compared an antisense oligonucleotide (ASO) inhibitor of CETP against the small-molecule CETP inhibitor anacetrapib in hyperlipidemic, CETP-transgenic, LDL receptor-knockout mice. Both drugs produced comparable reductions in total plasma cholesterol and CETP activity and comparable increases in HDL cholesterol. However, only the antisense-treated mice showed an enhanced effect on macrophage reverse cholesterol transport, an effect the authors attribute to differences in HDL apolipoprotein composition and to plasma triglyceride reductions specific to the antisense approach. The ASO-mediated reduction in CETP mRNA was also associated with less aortic cholesterol accumulation than seen with anacetrapib, suggesting CETP antisense oligonucleotides may offer functional advantages over small-molecule CETP inhibition and supporting their continued development as a cardiovascular therapy.
Original abstract
Due to their ability to promote positive effects across all of the lipoprotein classes, cholesteryl ester transfer protein (CETP) inhibitors are currently being developed as therapeutic agents for cardiovascular disease. In these studies, we compared an antisense oligonucleotide (ASO) inhibitor of CETP to the CETP small molecule inhibitor anacetrapib. In hyperlipidemic CETP transgenic (tg) mice, both drugs provided comparable reductions in total plasma cholesterol, decreases in CETP activity, and increases in HDL cholesterol. However, only mice treated with the antisense inhibitor showed an enhanced effect on macrophage reverse cholesterol transport, presumably due to differences in HDL apolipoprotein composition and decreases in plasma triglyceride. Additionally, the ASO-mediated reductions in CETP mRNA were associated with less accumulation of aortic cholesterol. These preliminary findings suggest that CETP ASOs may represent an alternative means to inhibit that target and to support their continued development as a treatment for cardiovascular disease in man.
anacetrapibthe classmechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.