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TVB-2640 (FASN inhibitor) for the treatment of nonalcoholic steatohepatitis: FASCINATE-1, a randomized, placebo-controlled phase 2a trial

The study was designed as proof of concept for NNMT as a drug-development target

Jin Sung links brain fog and memory lapses to chronic inflammation from everyday foods, especially gluten

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

Researchers wanted to isolate just the fat-burning signal and AOD-9604 was the result