AGI-6780

AGI-6780 is a potent, selective, and cell-permeable small-molecule inhibitor of the mitochondrial enzyme **isocitrate dehydrogenase 2 (IDH2)**. It specifically targets the **R140Q** mutant form of IDH2 by binding to the allosteric site at the dimer interface, which stabilizes the enzyme in an open conformation and prevents the conversion of alpha-ketoglutarate (α-KG) to the oncometabolite **R-2-hydroxyglutarate (2-HG)**. Developed by **Agios Pharmaceuticals**, AGI-6780 has been primarily utilized as a tool compound to demonstrate that inhibiting mutant IDH2 can induce cellular differentiation in acute myeloid leukemia (AML) cells. Recent research has also explored its utility in solid tumors, such as **triple-negative breast cancer**, where it appears to synergize with proteasome inhibitors to disrupt metabolic-proteostatic balance and induce apoptosis.