AI Article Synopsis
- Glutathione peroxidase 4 (GPX4) is a potential cancer therapy target, as it helps reduce harmful lipid peroxides within cells.
- Some cancer cells do not respond well to existing GPX4 inhibitors, prompting a search for compounds that work better in combination.
- The study discovered a compound named NPD4928 that boosts the effectiveness of GPX4 inhibitors and targets ferroptosis suppressor protein 1, indicating its potential for improving cancer treatment through inducing ferroptosis.
Article Abstract
Glutathione peroxidase 4 (GPX4) is an intracellular enzyme that oxidizes glutathione while reducing lipid peroxides and is a promising target for cancer therapy. To date, several GPX4 inhibitors have been reported to exhibit cytotoxicity against cancer cells. However, some cancer cells are less sensitive to the known GPX4 inhibitors. This study aimed to explore compounds showing synergistic effects with GPX4 inhibitors. We screened a chemical library and identified a compound named NPD4928, whose cytotoxicity was enhanced in the presence of a GPX4 inhibitor. Furthermore, we identified ferroptosis suppressor protein 1 as its target protein. The results indicate that NPD4928 enhanced the sensitivity of various cancer cells to GPX4 inhibitors, suggesting that the combination might have therapeutic potential via the induction of ferroptosis.
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| http://dx.doi.org/10.1021/acschembio.2c00028 | DOI Listing |
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