5-Amino-1MQ

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small molecule, not a peptide: a compact N-methylated quinolinium cation with the formula C10H11N2+ and a mass of 159.21 g/mol. It belongs to the methylquinolinium series that emerged from structure-activity work on inhibitors of nicotinamide N-methyltransferase (NNMT), a cytosolic enzyme that N-methylates nicotinamide and a range of xenobiotics. Within that series, quinoliniums with primary amine substitutions were identified as a scaffold combining low-micromolar NNMT inhibition with high membrane permeability.

5-Amino-1MQ in the research literature

Structure-activity screening placed methylquinoliniums among the most active NNMT inhibitor scaffolds, with IC50 values near 1 micromolar, and docking studies predicted selective binding to the enzyme's nicotinamide substrate site. In cultured adipocytes, this class reduced the NNMT product 1-methylnicotinamide, raised intracellular NAD+ and S-adenosylmethionine and suppressed lipogenesis, while showing no inhibition of related SAM-dependent methyltransferases or NAD+ salvage pathway enzymes.

In rodent work, NNMT inhibition has been studied in diet-induced mouse models of energy balance, and in aged-mouse models of skeletal muscle regeneration, where increased muscle stem cell proliferation and fusion were reported alongside C2C12 myoblast differentiation and NAD+/NADH redox shifts in vitro. A validated LC-MS/MS assay for quantifying 5-amino-1MQ in rat plasma and urine has supported pharmacokinetic characterization of the compound.