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GST P1-1 inhibitors are typically non-productive analogues of glutathione which covers broad chemical space; hence it is likely that several clinically used drugs may unknowingly act as GST P1-1 inhibitors. We developed a high-throughput screening assay for GST P1-1 and screened 5830 compounds. From the screening, 24 potent GST P1-1 inhibitors were identified and assessed for cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cell lines. Ethacrynic acid (a known GST P1-1 inhibitor), ZM 39923, PRT 4165, 10058-F4, and cryptotanshinone were shown to be the most active. A competitive GST P1-1 assay was performed to identify the inhibition type of these five compounds. Another <jats:italic>in vitro<\/jats:italic> cytotoxicity experiment was conducted to explore the differences in the cytotoxicity profiles of the combinations tested. Western blot analysis was used to identify the presence of GST P1-1 in the breast cancer cell lines tested. The implications of these results concerning alternative treatment options for breast cancers are discussed.<\/jats:p>","DOI":"10.1371\/journal.pone.0319904","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T17:34:52Z","timestamp":1753378492000},"page":"e0319904","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of glutathione transferase (GST P1) inhibitors via a high-throughput screening assay and implications as alternative treatment options for breast cancers"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-9868","authenticated-orcid":true,"given":"Sarah A. 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