II399 is a potent, selective NNMT bisubstrate inhibitor containing an unconventional SAM mimic, with a K i of 5.9 nM. II399 exhibits an explicit pattern of competitive inhibition for NAM. II399 occupies both the substrate and cofactor binding pockets. II399 has the potential for the research of cancers, metabolic, cardiovascular, and neurodegenerative diseases.
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