Temozolomide (TMZ) is an orally ADMINISTERED alkylating agent of the imidazotetrazine class that is chemically RELATED to dacarbazine. It is rapidly and completely absorbed and passes through the blood-brain barrier, creating cerebrospinal fluid concentrations that are 20% to 40% of plasma levels. The DNA repair PROTEIN MGMT removes alkyl groups from the O6 position of guanine, a target of alkylating agents, such as TMZ. In tumors, high expression of MGMT has been associated with resistance to treatment with alkylating agents. Inactivation of the MGMT gene by PROMOTER methylation diminishes DNA repair activity and has been associated with longer overall survival in patients with GBM who are treated with alkylating agents.

Temozolomide (TMZ) is an orally administered alkylating agent of the imidazotetrazine class that is chemically related to dacarbazine. It is rapidly and completely absorbed and passes through the blood-brain barrier, creating cerebrospinal fluid concentrations that are 20% to 40% of plasma levels. The DNA repair protein MGMT removes alkyl groups from the O6 position of guanine, a target of alkylating agents, such as TMZ. In tumors, high expression of MGMT has been associated with resistance to treatment with alkylating agents. Inactivation of the MGMT gene by promoter methylation diminishes DNA repair activity and has been associated with longer overall survival in patients with GBM who are treated with alkylating agents.