– 4-Chloropyridine acts as an inhibitor of Nicotinamide N-methyltransferase (NNMT). Serving as a substrate for NNMT, this compound enhances the electrophilicity at the C4 position through methylation of the pyridine nitrogen. This modification facilitates an aromatic nucleophilic substitution reaction with the non-catalytic cysteine (C159) in NNMT, ultimately leading to suicidal activity inhibition of the enzyme. 4-Chloropyridine is a promising candidate for the development of activity-based probes targeting NNMT functions.