Vorasidenib

DB17097ApprovedInvestigationalSmall moleculeIsocitrate Dehydrogenase 1 Inhibitor Isocitrate Dehydrogenase 2 Inhibitor

Vorasidenib is a isocitrate dehydrogenase type 1 (IDH1) and 2 (IDH2) inhibitor used to treat Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. It works by suppressing the levels of D-2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH1 and IDH2 isoforms.

Mechanism: Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes can be identified in various malignancies, including acute myeloid leukemia (AML) and gliomas. Mutant enzymes produce an oncometabolite D-2-hydroxyglutarate (2-HG), which contributes to oncogenesis and tumour growth by blocking the activity of α-ketoglutarate–dependent enzymes and causing epigenetic dysregulation, such as global DNA hypermethylation, and interfering with immunity.
Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild-type and mutant variants, including R132H and the IDH2 wild-type and mutant variants. In cell-based and in vivo tumour models expressing IDH1 or IDH2 mutated proteins, vorasidenib decreased the production of 2-2-HG and partially restored cellular differentiation.
Curator reviewed · 8 references
Primary indication: Vorasidenib is indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation following surgery including...Curator reviewed · 4 structured indications
Formula / weight: C₁₄H₁₃ClF₆N₆ · 414.74 g/mol (avg)
First approval: Canada, 2024 · United States, 2024 · European Union, 2025
Code names: AG-881 · S095032
Brand names: Voranigo