Acute myelogenous leukemia (AML) Isocitrate dehydrogenase 2 (IDH2) Patient sample and in vitro studies suggest mutant-selective IDH2 inhibitors could help treat patients with IDH2-mutant AML. In in vitro assays, AGI-6780 inhibited mutant IDH2 with nanomolar potency and selectivity over the wild-type enzyme. In primary human AML cells with mutant IDH2, AGI-6780 decreased levels of the (R)-enantiomer of 2-hydroxyglutarate (2-HG), an oncometabolite produced specifically by the mutant enzyme, and

more »

... creased leukemic cell differentiation compared with vehicle. Next steps include further preclinical development of mutant IDH2 inhibitors in preparation for clinical trials in patients who have IDH2-mutant AML. Agios Pharmaceuticals Inc. has preclinical programs targeting IDH1 and IDH2 in cancers with mutations in the metabolic enzymes.