N-methyl-2-pyridone-5-carboxamide

N-methyl-2-pyridone-5-carboxamide (2PY) is a major terminal metabolite of nicotinamide (vitamin B3) metabolism, formed through the oxidation of N1-methylnicotinamide by the enzyme aldehyde oxidase 1 (AOX1). While historically considered an inert end-product, recent research has identified 2PY as a pro-steatotic and pro-atherogenic mediator. Elevated plasma levels of 2PY are intricately linked to non-alcoholic fatty liver disease (NAFLD) and an increased susceptibility to atherosclerotic cardiovascular disease (ASCVD). Mechanistically, 2PY has been shown to reprogram macrophage lipid metabolism by upregulating ELOVL fatty acid elongase 6 (ELOVL6), which facilitates foam cell formation and the progression of atherosclerosis. In preclinical models, administration of 2PY aggravates lipid metabolic dysbiosis, hepatic steatosis, and plaque formation.

Other names

1-methyl-2-pyridone-5-carboxamide1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamideN1-methyl-2-pyridone-5-carboxamideN-1-methyl-2-pyridone-5-carboxamideN 1-methyl-2-pyridone-5-carboxamide