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Despite its therapeutic efficacy, tacrolimus has a narrow therapeutic window (520 ng/mL whole blood 1012 h post-dose) and frequently displays episodes of toxicity, such as nephrotoxicity, neurotoxicity, and glucose intolerance (Chow et al., 1997)
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Alteration of several metabolic enzymes and pathways that affect KG abundance and KGDD activity have been reported in cancer, such as mutations of the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), changes in glutaminolysis that deplete KG, and alterations in fumarate hydratase and succinate dehydrogenase that inhibit KGDD activity 11
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