Online now: Jia et al. reveal that KRAS-mutant leukemic cells, which express low SLC25A51 protein, are selectively killed by 615 through reducing mitochondrial NAD+. 615 simultaneously binds to and inhibits both SLC25A51, a mitochondrial NAD+ importer, and SDHA, an ETC component. It further reduces SLC25A51 protein by decreasing K264 succinylation, thereby depleting mitochondrial NAD+.