4-Chloropyridine

4-Chloropyridine is an inhibitor of nicotinamide N-methyltransferase (NNMT) . It can act as a substrate for NNMT and, during its catalytic reaction, enhances the electrophilicity of the C4 position by methylating the nitrogen atom of the pyridine ring. This promotes an aromatic nucleophilic substitution reaction with the non-catalytic cysteine (C159) in NNMT, ultimately leading to the suicide inhibition of NNMT's activity. 4-Chloropyridine holds potential for the development of NNMT activity-based probes [1].