Temozolomide

Temozolomide (NSC 362856, CCRG 81045) is a DNA methylating agent used for the treatment of Grade IV astrocytoma. Temozolomide exhibits schedule-dependent antineoplastic activity by interfering with DNA replication. Temozolomide displays antitumor activity against a board spectrum of tumors, including leukemias, lymphomas and solid tumors (IC50 = 5.0 μM for cytotoxicity against mouse TLX5 lymphoma cells). Temozolomide induces G2/M arrest and apoptosis through adduction of a methyl group to O6 position of guanine in genomic DNA and functional inactivation of DNA repair protein O(6)-alkylguanine DNA alkyltransferase (AGT) in base excision repair (BER) pathway. Temozolomide treatment triggered ER stress with increased expression of GADD153 and GRP78 proteins, and deceased pro-caspase 12 protein. Temozolomide is currently in a phase II clinical trial in the treatment of melanoma.