AGI-5198

AGI-5198 is a potent and selective small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1), specifically targeting the R132H mutation. Developed by Agios Pharmaceuticals, it was one of the first compounds to demonstrate that pharmacological inhibition of mutant IDH1 could effectively lower levels of the oncometabolite D-2-hydroxyglutarate (D-2HG), which is produced in high quantities by mutant IDH1 and contributes to oncogenesis. Preclinical studies showed that AGI-5198 induces cellular differentiation and inhibits the growth of IDH1-mutant glioma cells and xenografts. According to research reports, the compound has been advanced into clinical evaluation for patients with IDH1-mutant glioblastomas. It is also widely used as a chemical probe to study the metabolic and epigenetic consequences of IDH mutations, such as alterations in phospholipid levels and one-carbon metabolism.