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Food Chem Toxicol 60:369376 Tonelli C, Chio IIC, Tuveson DA (2018) Transcriptional regulation by Nrf2

At the molecular level, 5-amino-1MQ functions as a competitive inhibitor of NNMT, demonstrating remarkable potency with an IC of 1.2 0.1 M under standard assay conditions (50 M SAM, 100 M 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

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M.IllanesO.OrselK.WolfR.et al

Expert: Zuri Hempill-Bryant, MD, Studies: Goraya JS, Kaur S, Mehra B