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Synonym: 5-Amino-1MQ, NNMTi, 5-Amino-1-methylquinolinium iodide

Additionally, analogues containing the quinolinium scaffold lacked inhibitory activity against enzymes in the NAD + salvage pathway that bind nicotinamide-containing substrate, including NAMPT[27, 32] and the NAD + -dependent SIRT1 enzyme, which deacetylates NAD + to produce NA, a product inhibitor of SIRT1.[33] These results suggest that quinolinium-based NNMT inhibitors achieve selectivity by specifically interacting with the NA-binding pocket of NNMT,[17] unlike several known non-selective methyltransferase inhibitors that interact with the SAM-binding pocket, which is highly conserved among SAM-dependent methyltransferases.[34, 35] Membrane-permeable NNMT inhibitors reduced intracellular 1-MNA levels in a concentration-dependent manner and at pharmacologically relevant concentrations that did not impact cell viability, suggesting these small molecules interact directly with NNMT in cells

To explore whether GSDMD in HCs plays a role in NIHL, Gsdmd -HC-cKO mice were generated using Cre recombinase expressed via the AAV.PHP.eB serotype, which has high transfection efficiency in HCs 23

Heimbrger, S

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