AIMS: Life expectancy is typically reduced by 2-4 years in people with a body mass index (BMI) of 30-35 kg/m MAIN METHODS: Herein we performed in silico computational modelling of a compound library of ∼53,000 molecules to identify carnosine-like molecules with intrinsic resistance to carnosinase turnover. KEY FINDINGS: We show that leading candidate molecules reduced reactive species in C2C12 myotubes, and that mice fed N-methyl-[6-(2-furyl)pyrid-3-yl]methylamine alongside a high fat diet had significantly decreased amounts of damaging plasma 4-hydroxynonenal and 3-nitrotyrosine reactive species. Oral administration of N-methyl-[6-(2-furyl)pyrid-3-yl]methylamine to high fat-fed mice also resulted in a modest ∼10 % reduction in weight gain when compared to mice fed only high fat diet. SIGNIFICANCE: Our findings suggest that inhibition of carnosinase enzymes can increase the life-span, and thereby enhance the efficacy, of endogenous carnosine in vivo, thereby offering potential therapeutic benefits against obesity and other cardiometabolic diseases characterised by metabolic stress.