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These therapies may not be appropriate for individuals who are pregnant or breastfeeding, have certain chronic medical conditions, active cancer, or known allergies to components of the injections
[DOI] [PMC free article] [PubMed] [Google Scholar] 65.Fadilah NIM, Phang SJ, Kamaruzaman N, Salleh A, Zawani M, Sanyal A
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
