5-Amino-1MQ (5-amino-1-methylquinolinium) is a synthetic small molecule that selectively inhibits Nicotinamide N-methyltransferase (NNMT)[1]. NNMT is a cytosolic enzyme that methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. In states of obesity and metabolic dysfunction, NNMT is often overexpressed in adipose tissue, depleting nicotinamide and reducing NAD+ availability[2]. By inhibiting NNMT, 5-Amino-1MQ may spare nicotinamide for NAD+ synthesis via the salvage pathway, thereby activating SIRT1 (Sirtuin 1) pathways associated with mitochondrial biogenesis, fat oxidation, and metabolic flexibility[3]. Preclinical studies indicate that NNMT knockdown or inhibition can protect against diet-induced weight gain and improve metabolic parameters without reducing food intake[8][9].
