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Decitabine

Dacogen

DNA methyltransferase inhibitor (hypomethylating agent)

Evidence Score

50

preclinical
Mechanism of Action

Deoxycytidine analog that incorporates into DNA during replication and traps DNMTs, leading to their depletion. More potent DNA demethylator than azacitidine. Could reverse the CIMP phenotype characteristic of SDH-deficient tumors.

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

DNMT1

DNA methyltransferase 1

downstream

Maintenance DNA methyltransferase. Contributes to hypermethylation phenotype. Target of azacitidine and decitabine.

UniProt: P26358

DNMT3A

DNA methyltransferase 3A

downstream

De novo DNA methyltransferase. Works with DNMT1 to establish aberrant methylation patterns.

UniProt: Q9Y6K1

Quick Facts
FDA Approved

Approved Indications

  • Myelodysplastic syndromes
ChEMBL IDCHEMBL1201129
PubChem CID451668
Evidence

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

Coming in Phase 3

AI Analysis

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