Journal
ACS CHEMICAL BIOLOGY
Volume 17, Issue 2, Pages 483-491Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.2c00028
Keywords
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Categories
Funding
- Molecular Profiling Committee
- AMED P-CREATE [JP20 cm0106112h0005]
- [JP17H06412]
- [JP16H06276]
- [JP18H05503]
- [JP21H04720]
- [JP20H05620]
- [JP20K05857]
- [JP19K05746]
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The compound NPD4928 was identified to enhance the sensitivity of various cancer cells to GPX4 inhibitors, potentially having therapeutic potential via the induction of ferroptosis.
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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