ANGPTL3

Class

ANGPTL3 inhibitor (monoclonal antibody)

ANGPTL3 (angiopoietin-like 3) is a liver-secreted protein that inhibits two enzymes central to lipid processing: lipoprotein lipase and endothelial lipase. By restraining these enzymes, ANGPTL3 normally limits the breakdown of triglyceride-rich lipoproteins and the metabolism of certain lipoprotein particles in the bloodstream. When ANGPTL3 is blocked or removed, lipoprotein lipase activity increases, accelerating clearance of triglycerides and, through downstream effects on lipoprotein particle metabolism, lowering LDL cholesterol as well. This makes ANGPTL3 an attractive target for lowering multiple types of atherogenic lipids simultaneously, which is relevant in severe inherited disorders of cholesterol and triglyceride metabolism, as well as in broader cardiovascular risk reduction where standard lipid-lowering approaches are insufficient or not tolerated. Notably, individuals with naturally occurring loss-of-function mutations in ANGPTL3 have markedly reduced lipid levels and do not appear to suffer obvious harm, which has supported confidence in pursuing this target pharmacologically. A range of modalities has been developed against ANGPTL3, including antibodies that neutralize the circulating protein, small interfering RNA and gene-editing approaches that reduce its production in the liver, and small molecules, reflecting different strategies for achieving durable suppression of this pathway.