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NAD+ metabolism enzyme NNMT in cancer-associated fibroblasts drives immune evasion in urothelial carcinoma by elevating PD-L1 N-glycosylation
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NNMT is an enzyme that grabs nicotinamide and methylates it, turning it into a waste product called 1-MNA that gets cleared from the body
5-Amino-1MQ Key Research Facts Chemical name: 5-Amino-1-Methylquinolinium (also abbreviated as 5A-1MQ or 5MQ) Target enzyme: Nicotinamide N-Methyltransferase (NNMT) Mechanism: Competitive inhibition of NNMT reduces 1-MNA production, preserves nicotinamide for NAD+ synthesis and SAM for epigenetic methylation Selectivity: High selectivity for NNMT does not inhibit related SAM-dependent methyltransferases or NAD+ salvage pathway enzymes Membrane permeability: High passive and active transport permeability confirmed in PAMPA and Caco-2 cell assays NNMT expression: Upregulated in obese adipose tissue, multiple cancer types, and aged skeletal muscle tissue contexts of primary research interest Downstream targets: NAD+ availability, SIRT1/SIRT3 activity, SAM-dependent epigenetic methylation, lipogenesis, energy expenditure Pre-clinical models: Diet-induced obese (DIO) mice, 3T3-L1 adipocyte cell models, aged mouse skeletal muscle models, HeLa cancer cell lines In vitro cell viability: No impact on cell viability at 10 M concentration in 3T3-L1 pre-adipocytes in published toxicity profiling What Does 5-Amino-1MQ Do in Research
Human clinical trial activity is emerging but limited
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