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Temozolomide

Temodar, Temodal

Alkylating agent

Evidence Score

68

clinical trial
Mechanism of Action

Prodrug that alkylates DNA at guanine O6 and N7 positions. SDH-deficient tumors with SDHB loss show epigenetic silencing of MGMT (DNA repair gene) due to promoter hypermethylation, potentially increasing sensitivity to temozolomide.

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

Quick Facts
FDA Approved

Approved Indications

  • Glioblastoma multiforme
  • Anaplastic astrocytoma
ChEMBL IDCHEMBL810
PubChem CID5394
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.