6-benzylguanine

6-benzylguanine is a synthetic guanine analogue and small molecule antineoplastic agent. It acts as an irreversible inhibitor of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT), also known as methylguanine DNA methyltransferase (MGMT). By transferring its benzyl group to the active-site cysteine of AGT, it inactivates the enzyme, thereby preventing AGT-mediated repair of alkylated DNA lesions. This inhibition sensitizes tumor cells to alkylating agents such as temozolomide and carmustine by blocking their primary resistance mechanism. Clinically, it has been investigated primarily in combination with alkylating chemotherapy for glioblastoma and other solid tumors but was found to increase toxicity without significant benefit when combined with temozolomide. It is also widely used as a biochemical tool in research on DNA repair mechanisms[1][3][5][9].

Other names

6-(benzyloxy)-7H-purin-2-aMine6-benzyloxy guanineO6-BenzyLO-6-BenzyLO 6-BenzyL