Vorasidenib is a synthetic small-molecule pharmaceutical active ingredient that acts as a dual inhibitor of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2). It is designed to inhibit both mutant and wild-type forms of IDH1 and IDH2, thereby reducing the production of the oncometabolite 2-hydroxyglutarate (2-HG).
Vorasidenib is marketed under the brand name Voranigo. The FDA approved vorasidenib in August 2024 for adult and pediatric patients aged 12 years and older with Grade 2 astrocytoma or oligodendroglioma carrying a susceptible IDH1 or IDH2 mutation following surgery.
Vorasidenib has the molecular formula C₁₄H₁₃ClF₆N₆ for the active moiety and a molecular weight of approximately 423.7 g/mol. Its CAS Number is 1644545-52-7 and its FDA UNII is 789Q85GA8P.
In the approved drug product, vorasidenib is present as a hemicitric acid hemihydrate co-crystal. The molecular formula of this form is C₁₄H₁₃ClF₆N₆ · ½C₆H₈O₇ · ½H₂O, with a molecular weight of 519.8 g/mol. FDA describes the material as a white to off-white solid that is practically insoluble in aqueous solutions from pH 1.2 to 6.8.
Vorasidenib inhibits IDH1 and IDH2 enzymes. Mutations in IDH1 or IDH2 can result in abnormal production of 2-hydroxyglutarate. Vorasidenib reduces 2-HG production in IDH-mutated tumor models and is designed to interfere with the metabolic effects associated with these mutations.
Vorasidenib is a chemically synthesized small molecule requiring controlled manufacturing and purification processes. Important manufacturing considerations include control of starting materials, intermediates, process-related impurities, stereochemical characteristics, residual solvents and final API purity.
The final active substance should undergo validated analytical testing for identity, assay, related substances and other applicable critical quality attributes before pharmaceutical use.
Vorasidenib API can be characterized using chromatographic and spectroscopic techniques. HPLC or UPLC methods can be used for assay and impurity determination, while spectroscopic techniques such as IR and mass spectrometry can support identity confirmation.
Additional analytical controls may include residual-solvent determination, water content, elemental impurities, particle-size distribution and solid-state characterization. The appropriate acceptance criteria should correspond to the validated API specification.
Vorasidenib is primarily associated with pharmaceutical development for IDH1- and IDH2-mutated gliomas. The FDA-approved indication covers Grade 2 astrocytoma and oligodendroglioma with a susceptible IDH1 or IDH2 mutation in patients aged 12 years and older following surgery.
Vorasidenib API is therefore relevant to oncology pharmaceutical research, formulation development and manufacturing of IDH-targeted therapies.
Important quality attributes for Vorasidenib API include chemical identity, assay, related substances, stereochemical purity where applicable, residual solvents, water content, elemental impurities and solid-state properties.
Because Vorasidenib is a relatively new pharmaceutical substance, numerical API release limits should be taken from the applicable approved or validated drug-substance specification rather than estimated generic API limits.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 99.0% |
| Individual Impurity | NMT 0.50% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 2.0% |
| Solubility | Practically insoluble in aqueous solutions from pH 1.2 to 6.8 |