QSAR and Chemical Read-Across Analysis of 370 Potential MGMT Inactivators to Identify the Structural Features Influencing Inactivation Potency.

ABSTRACT: O⁶-methylguanine-DNA methyltransferase (MGMT) constitutes an important cellular mechanism for repairing potentially cytotoxic DNA damage induced by guanine O⁶-alkylating agents and can render cells highly resistant to certain cancer chemotherapeutic drugs. A wide variety of potential MGMT inactivators have been designed and synthesized for the purpose of overcoming MGMT-mediated tumor resistance. We determined the inactivation potency of these compounds against human recombinant MGMT using [³H]-methylated-DNA-based MGMT inactivation assays and calculated the IC₅₀ values. Using the results of 370 compounds, we performed quantitative structure-activity relationship (QSAR) modeling to identify the correlation between the chemical struc

SUBMITTER: Sun G 

PROVIDER: S-EPMC10458236 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature