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BI-4916, a prodrug of the cofactor nicotinamide adenine dinucleotide (NADH/NAD+)-competitive PHGDH inhibitor BI-4924, has shown high selectivity against the majority of other dehydrogenase targets. An intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid-based drug to overcome high cytosolic levels of the competitive cofactors NADH/NAD+.
