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Enasidenib

Idhifa

IDH2 inhibitor

Evidence Score

28

theoretical
Mechanism of Action

Selective inhibitor of mutant IDH2, which produces the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG and succinate share the same mechanism of action (inhibiting α-KG-dependent dioxygenases). Insights from IDH-targeted therapy may inform SDH-deficient approaches.

Pathway Connections
Epigenetic Dysregulation

Succinate inhibits TET family DNA demethylases and Jumonji-domain histone demethylases, causing global DNA and histone hypermethylation. This silences tumor suppressors and blocks differentiation.

Upstream event:

Succinate inhibits TET1/2/3 and KDM histone demethylases

Downstream effects:

DNA hypermethylation (CIMP phenotype)5-hydroxymethylcytosine lossTumor suppressor silencingHistone hypermethylationDifferentiation block
Molecular Targets

IDH1

Isocitrate dehydrogenase 1

metabolic

Produces α-KG. IDH mutations produce 2-HG (oncometabolite analogous to succinate). Cross-pathway therapeutic insights.

UniProt: O75874

Quick Facts
FDA Approved

Approved Indications

  • IDH2-mutated acute myeloid leukemia
ChEMBL IDCHEMBL3989808
PubChem CID89683805
Evidence

Evidence from PubMed, OpenTargets, and ChEMBL will appear here once external data integration is enabled.

Coming in Phase 3

For research exploration only — not medical advice. Consult your doctor before acting on any information.

AI Analysis

Have Claude analyze this drug's repurposing potential for SDH-deficient diseases.