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[6] Frias, J.P., et al

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At the molecular level, 5-amino-1MQ functions as a competitive inhibitor of NNMT, demonstrating remarkable potency with an IC₅₀ of 1.2 ± 0.1 μM under standard assay conditions (50 μM SAM, 100 μM nicotinic acid). This represents a dramatic 10-fold improvement over the parent compound 1-methylquinolinium, achieved through strategic amino group substitution that enhances binding affinity to the NNMT active site. The compound's mechanism centers on preventing the methylation of nicotinamide to 1-methylnicotinamide (1-MNA), thereby preserving nicotinamide for recycling back to NAD+ through the salvage pathway. This intervention effectively blocks what researchers have termed the "NNMT metabolic drain" – a process that simultaneously depletes NAD+ precursors and consumes cellular methylation capacity