Vorasidenib Citrate

**Semantic type:** Pharmacologic Substance

**Definition:** The hemicitrate, hemihydrate form of vorasidenib, an orally available inhibitor of wild-type (WT) and mutated forms of both isocitrate dehydrogenase type 1 (IDH1, IDH1 [NADP+] soluble) in the cytoplasm and type 2 (IDH2, isocitrate dehydrogenase [NADP+], mitochondrial) in the mitochondria, with potential antineoplastic activity. Upon administration, vorasidenib specifically targets and inhibits WT and mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH1 or IDH2 mutations and/or overexpressing IDH1 or IDH2. In addition, vorasidenib is able to penetrate the blood-brain barrier (BBB). IDH1 and 2, metabolic enzymes that catalyze the conversion of isocitrate into a-KG, play key roles in energy production and are mutated in a variety of cancer cell types. In addition, mutant forms of IDH1 and 2 catalyze the formation of 2HG and drive cancer growth by blocking cellular differentiation and inducing cellular proliferation.

**Synonyms:** - VORASIDENIB HEMICITRIC ACID HEMIHYDRATE - Voranigo - Vorasidenib Hemicitric Acid Hemihydrate