Glutathione transferases as targets for cancer therapy.
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 GST-activated cytotoxic prodrugs. In the present review we discuss the current structural and pharmacological knowledge of both types of GST-targeting compounds.
Ruzza
Paolo
P
Institute of Biomolecular Chemistry of CNR, Padova, Italy. paolo.ruzza@unipd.it
Rosato
Antonio
A
Rossi
Carlo Riccardo
CR
Floreani
Maura
M
Quintieri
Luigi
L
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055162:Biocatalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D011355:Prodrugs / Q000627:therapeutic use; D011487:Protein Conformation
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011355:Prodrugs; D005982:Glutathione Transferase