The Sound of Evolution
Temozolomide
Mechanism of action:
Temozolomide is an alkylating agent and an imidazotetrazine derivative. At physiological pH, temozolomide undergoes spontaneous hydrolysis to form the active methylating intermediate MTIC (monomethyl triazeno imidazole carboxamide). MTIC adds methyl groups to DNA bases, primarily at O6-guanine, N7-guanine, and N3-adenine. This repeatedly triggers DNA repair cycles and ultimately leads to DNA strand breaks, cell cycle arrest, and apoptosis.
Reference(s):
1. Neyns B et al. (2010). Dose-dense temozolomide regimens: antitumor activity, toxicity, and immunomodulatory effects. Cancer.
2. Wick W et al. (2009). New (alternative) temozolomide regimens for the treatment of glioma. Neuro Oncol.
3. Villano JL et al. (2009). Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol.