idh305

IDH305 is an orally available, brain-penetrant, mutant-selective allosteric inhibitor of isocitrate dehydrogenase 1 (IDH1), specifically targeting the R132 mutation. It exhibits over 200-fold selectivity for mutant IDH1 isoforms compared to wild-type. By inhibiting mutant IDH1, it blocks the production of the oncometabolite 2-hydroxyglutarate (2-HG), which accumulates in cancers with this mutation and contributes to tumorigenesis. Developed by Novartis/Novartis Oncology, its primary indications have included low-grade glioma and acute myeloid leukemia (AML) with confirmed IDH1 R132 mutations. Clinical studies demonstrated target engagement and some clinical responses but also revealed a potentially narrow therapeutic window; development was suspended before a recommended phase 2 dose could be established[1][5][6][9].

Other names

IDH1(R132) inhibitor IDH305