NNMT Inhibitors

NNMT Inhibitors encompass a diverse range of compounds that, through various mechanisms, indirectly influence the activity of Nicotinamide N-methyltransferase (NNMT), a key enzyme in nicotinamide and pyridine metabolism. Unlike direct enzyme inhibitors, these compounds primarily function by altering the metabolic and cellular environment in which NNMT operates, thus affecting its activity. For example, 3-Deazaneplanocin A (DZNep) acts as an inhibitor of S-adenosylhomocysteine hydrolase, leading to an accumulation of S-adenosylhomocysteine, which can competitively inhibit NNMT by interfering with its methyl donor, S-adenosylmethionine (SAMe). Similarly, Nicotinamide Riboside, a vitamin B3 variant, enhances cellular NAD+ levels, reducing the availability of nicotinamide, NNMT's substrate, thereby influencing its activity. Other compounds such as Tranylcypromine and EGCG (Epigallocatechin gallate) exert their effects through broader metabolic pathways. By altering the metabolic landscape, these compounds can indirectly modulate NNMT activity, reflecting the complex interplay between metabolic states and enzymatic functions.

Further expanding this chemical class are compounds like Methylthioadenosine (MTA), a byproduct of polyamine synthesis, and Tenovin-6, a small molecule influencing sirtuins and cellular metabolic states. Both compounds could indirectly affect NNMT activity through their roles in cellular methylation processes and metabolic regulation. Resveratrol, Metformin, and Sulforaphane, each known for their impact on various aspects of metabolism, represent additional members of this class. Their broad actions on metabolic pathways provide a basis for their indirect influence on NNMT activity. Similarly, Curcumin, Chlorogenic Acid, and Quercetin, with their diverse effects on signaling pathways and cellular metabolism, add to the complexity of this class.