G6PDi-1 is a reversible and noncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PDH; IC50 = 0.07 µM), the enzyme that converts G6P to 6-phosphogluconolactone using NADP+ as a cofactor in the first step of the pentose phosphate pathway.1 G6PDi-1 (10 and 50 µM) reduces NADPH levels in a variety of cultured cells, including red blood cells and T cells. It decreases colony formation of HCT116 cells when used at concentrations of 20 and 30 µM, an effect that can be rescued by the antioxidant N-acetyl cysteine. G6PDi-1 decreases the production of cytokines induced by phorbol 12-myristate 13-acetate and ionomycin in T cells and prevents PMA-induced oxidative burst in neutrophils.
1.Ghergurovich, J.M., GarcÍa-CaÑaveras, J.C., Wang, J., et al.A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathwayNat. Chem. Biol.16(7)731-739(2020)