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Updated: Aug 13, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Glutathione S-transferases as regulators of kinase pathways and anticancer drug targets
Danyelle M Townsend1, Victoria L Findlay, Kenneth D Tew
1Medical University of South Carolina, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Charleston, South Carolina, USA.
Abstract:
Anticancer drug development using the platform of glutathione (GSH), glutathione S-transferases (GST) and pathways that maintain thiol homeostasis has recently produced a number of lead compounds. GSTpi is a prevalent protein in many solid tumors and is overexpressed in cancers resistant to drugs. It has proved to be a viable target for pro-drug activation with at least one candidate in late-stage clinical development. In addition, GSTpi possesses noncatalytic ligand-binding properties important in the direct regulation of kinase pathways. This has led to the development and testing of agents that bind to GSTpi and interfere with protein-protein interactions, with the phase II clinical testing of one such drug. Attachment of glutathione to acceptor cysteine residues (glutathionylation) is a posttranslational modification that can alter the structure and function of proteins. Two agents in preclinical development (PABA/NO, releasing nitric oxide on GST activation, and NOV-002, a pharmacologically stabilized pharmaceutical form of GSSG) can lead to glutathionylation of a number of cellular proteins. The biological significance of these modifications is linked with the mechanism of action of these drugs. In the short term, glutathione-based systems should continue to provide viable targets and a platform for the development of novel cancer drugs.
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