5-Amino-1MQ

What Is 5-Amino-1MQ?

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule selective inhibitor of nicotinamide N-methyltransferase (NNMT). It is a quinolinium-class compound rather than a peptide, grouped with the metabolic and longevity compounds because of the pathways it acts on. NNMT methylates nicotinamide, an NAD+ precursor, into 1-methylnicotinamide for excretion, and in doing so consumes S-adenosylmethionine, the cell's principal methyl donor. Adipose tissue from obese animals expresses NNMT at markedly higher levels than lean tissue, and elevated NNMT activity is associated with a storage-biased adipocyte phenotype.

When NNMT is inhibited, nicotinamide is recycled toward NAD+ synthesis rather than excreted, intracellular NAD+ rises, S-adenosylmethionine is spared, and adipocyte gene expression shifts toward oxidative metabolism. Reported downstream effects include increased polyamine flux, higher energy expenditure, and stabilised SIRT1 activity, since 1-methylnicotinamide normally suppresses SIRT1. In the foundational Neelakantan et al. (2019) study, diet-induced obese mice treated with 5-Amino-1MQ lost fat mass and showed roughly 30% smaller adipocytes with no change in food intake, which points to a metabolic shift rather than appetite suppression. No human randomised controlled trial data exist; the evidence base is preclinical.