vorasidenib   Click here for help

GtoPdb Ligand ID: 10663

Synonyms: AG-881 | AG881
PDB Ligand
Compound class: Synthetic organic
Comment: Vorasidenib (AG-881) inhibits mutant forms of the isocitrate dehydrogenases (IDH1 and IDH2) [3] 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 [4]. Vorasidenib can cross the blood brain barrier, and is being proposed as a chemotherapeutic for IDH mutation +ve cancers including gliomas [2,8] 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 [3,5]. The X-ray structures show that vorasidenib binds at an allosteric pocket formed in IDH homodimers, at the interface of the two monomers.
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. 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.

✖
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
SMILES / InChI / InChIKey
Click here for help

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.

✖
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
No information available.
Summary of Clinical Use Click here for help
Vorasidenib (AG-881) is being developed by Agios Pharmaceuticals and it has progressed to Phase 3 evaluation in patients with low grade IDH mutant +ve glioma, and has completed a Phase 1 trial for advanced hematologic malignancies with IDH1 or 2 mutations. Vorasidenib was issued orphan drug designation by the EMA in January 2023, as a treatment for glioma.
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. 7
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 6