enasidenib   Click here for help

GtoPdb Ligand ID: 8960

Synonyms: AG-221 | CC-90007 | Idhifa®
Approved drug PDB Ligand
enasidenib is an approved drug (FDA (2017))
Compound class: Synthetic organic
Comment: Enasidenib (AG-221) is an orally available inhibitor of isocitrate dehygrogenase 2 (IDH2), that is approved as an antineoplastic agent. This compound is example 409 in patent US20130190287 A1 [1].

enasidenib 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 8
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 108.74
Molecular weight 473.14
XLogP 3.02
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 CC(CNc1nc(Nc2ccnc(c2)C(F)(F)F)nc(n1)c1cccc(n1)C(F)(F)F)(O)C
Isomeric SMILES CC(CNc1nc(Nc2ccnc(c2)C(F)(F)F)nc(n1)c1cccc(n1)C(F)(F)F)(O)C
InChI InChI=1S/C19H17F6N7O/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32)
InChI Key DYLUUSLLRIQKOE-UHFFFAOYSA-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
Having completed Phase 3 clinical evaluation, enasidenib (AG-221) was approved by the US FDA in August 2017 [2], for the treatment for IDH2 mutation positive acute myeloid leukemia (AML- see trial NCT02577406). The presence of IDH2 mutations must be confirmed using the companion diagnostic, RealTime IDH2 Assay.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
AG-221 is believed to prevent the formation of IDH2 homodimers by binding to the inter-subunit contact region. This action prevents the formation of functional dimers of mutant IDH2 enzymes which would produce the oncometabolite 2-HG.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02577406 An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation Phase 3 Interventional Celgene