Besides catalyzing the inactivation of various electrophile-producing anticancer agents via conjugation to the tripeptide glutathione, some cytosolic proteins belonging to the glutathione transferase (formerly glutatione-S-transferase; GST) superfamily are emerging as negative modulators of stress/drug-induced cell apoptosis through the interaction with specific signaling kinases. In addition, several data link the overexpression of some GSTs, in particular GSTP1-1, to both natural and acquired resistance to various structurally unrelated anticancer drugs. Tumor overexpression of these proteins has provided a rationale for the search of GST inhibitors and GSTactivated cytotoxic prodrugs. In the present review we discuss the current structural and pharmacological knowledge of both types of GST-targeting compounds.
Keywords: GST inhibitors, GST-activated prodrugs, cancer chemotherapy, anticancer drug resistance
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