vorasidenib   Click here for help

GtoPdb Ligand ID: 10663

Synonyms: AG-881 | AG881 | Voranigo®
Approved drug PDB Ligand
vorasidenib is an approved drug (FDA (2024))
Compound class: Synthetic organic
Comment: Vorasidenib (AG-881) inhibits mutant forms of the isocitrate dehydrogenases (IDH1 and IDH2) [4] that catalyse the generation of the oncogenic metabolite d-2-hydroxyglutarate (2-HG). This compound and others, and their use for treating cancer are claimed in patent US10028961 [5]. Vorasidenib can cross the blood-brain barrier, and is being proposed as a chemotherapeutic for IDH mutation +ve cancers including gliomas [3,9] and hematological malignancies [1]. X-ray cocrystal structures of vorasidenib with mutant IDH1 and mutant IDH2 have been deposited with the RCSB Protein Data Bank [4,6]. The X-ray structures show that vorasidenib binds at an allosteric pocket formed in IDH homodimers, at the interface of the two monomers.

vorasidenib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 75.62
Molecular weight 414.08
XLogP 4.99
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1cccc(n1)c1nc(nc(n1)N[C@@H](C(F)(F)F)C)N[C@@H](C(F)(F)F)C
Isomeric SMILES Clc1cccc(n1)c1nc(nc(n1)N[C@@H](C(F)(F)F)C)N[C@@H](C(F)(F)F)C
InChI InChI=1S/C14H13ClF6N6/c1-6(13(16,17)18)22-11-25-10(8-4-3-5-9(15)24-8)26-12(27-11)23-7(2)14(19,20)21/h3-7H,1-2H3,(H2,22,23,25,26,27)/t6-,7-/m1/s1
InChI Key QCZAWDGAVJMPTA-RNFRBKRXSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Vorasidenib (AG-881) was developed by Agios Pharmaceuticals and was progressed to Phase 3 evaluation in patients with low grade IDH mutant +ve glioma, and a Phase 1 trial for advanced hematologic malignancies with IDH1 or 2 mutations was conducted. Vorasidenib was issued orphan drug designation by the EMA in January 2023, as a treatment for glioma. The FDA issued full approval for vorasidenib as a post-surgical therapy for grade 2 astrocytoma or oligodendroglioma with susceptible IDH1 or IDH2 mutations in August 2024 [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02492737 Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation Phase 1 Interventional Agios Pharmaceuticals, Inc.
NCT04164901 Study of AG-881 in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) Phase 3 Interventional Agios Pharmaceuticals, Inc. 8
NCT02481154 Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation Phase 1 Interventional Servier 7