Nicotinamide adenine dinucleotide phosphate-dependent dehydrogenase (NADP-DH)

NADP-dependent dehydrogenases are a broad class of oxidoreductase enzymes that utilize nicotinamide adenine dinucleotide phosphate (NADP+/NADPH) as a cofactor to catalyze the transfer of electrons in metabolic reactions [UniProt, 2024]. These enzymes are essential for maintaining cellular redox homeostasis and providing the reducing power required for the biosynthesis of lipids and nucleotides, primarily through the production of NADPH [PubMed: 29247102]. Key members of this family, such as Isocitrate Dehydrogenase 1 and 2 (IDH1/2) and Glucose-6-Phosphate Dehydrogenase (G6PD), are critical therapeutic targets in oncology and hematology [Nature Reviews Cancer, 2017]. Mutations in IDH1 and IDH2 lead to the production of the oncometabolite 2-hydroxyglutarate, which promotes tumorigenesis in gliomas and acute myeloid leukemia; this has led to the clinical approval of inhibitors like ivosidenib and enasidenib [PubMed: 30044953]. Furthermore, G6PD is the rate-limiting enzyme of the pentose phosphate pathway, and its activity is vital for protecting cells against oxidative stress, making it a focus for both drug safety (due to deficiency-related hemolysis) and potential anti-cancer strategies [PubMed: 23541368].

Other names

NADP+-dependent dehydrogenasesNADPH-dependent dehydrogenasesNADP-linked dehydrogenasesNADP-dependent oxidoreductases

Inhibition of enzymatic activity to prevent the production of oncometabolites (e.g., 2-hydroxyglutarate) or to disrupt cellular redox balance and biosynthetic pathways [PubMed: 30044953, PubMed: 29247102].