O6-substituted guanine compounds and methods for depleting O6-alkylguanine-DNA alkyltransferase levels

摘要

O6-substituted guanine compounds of the formula <IMAGE> wherein R is a benzyl group or a substituted benzyl group, cause a depletion of O6-alkylguanine-DNA alkyltransferase (AGT) activity in mammalian cells. These compounds may be administered to a host so as to reduce AGT levels in tumor cells of the host in order to increase host responsiveness to anti-neoplastic alkylating agents, including chloroethylating agents, such as chloroethylnitrosoureas, for chemotherapeutic treatment of a number of neoplasms.