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[1] Unlike the folic acid derivative leucovorin, folic acid is not clinically useful in offsetting the action of folate reductase inhibitors because it requires the enzyme dihydrofolate reductase for activation

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They tested these inhibitors in cell and animal models. They reported changes in intracellular nicotinamide-related metabolites and examined the biological effects of NNMT inhibition under experimental conditions. These outcomes have increased scientific interest in NNMT biology