The specific role of O⁶-methylguanine-DNA methyltransferase inhibitors in cancer chemotherapy

The DNA repair protein, O 6 -methylguanine DNA methyltransferase (MGMT), can confer resistance to guanine O 6 -alkylating agents. Therefore, inhibition of resistant MGMT protein is a practical approach to increase the anticancer effects of such alkylating agents. Numerous small molecule inhibitors were synthesized and exhibited potential MGMT inhibitory activities. Although they were nontoxic alone, they also inhibited MGMT in normal tissues,...