2. Academic Validation
  3. Identification of a Small Molecule That Enhances Ferroptosis via Inhibition of Ferroptosis Suppressor Protein 1 (FSP1)

Identification of a Small Molecule That Enhances Ferroptosis via Inhibition of Ferroptosis Suppressor Protein 1 (FSP1)

  • ACS Chem Biol. 2022 Feb 18;17(2):483-491. doi: 10.1021/acschembio.2c00028.
Hiromasa Yoshioka 1,  Tatsuro Kawamura 2,  Makoto Muroi 1 2,  Yasumitsu Kondoh 1,  Kaori Honda 1,  Makoto Kawatani 1,  Harumi Aono 1,  Herbert Waldmann 3,  Nobumoto Watanabe 2,  Hiroyuki Osada 1 2
Affiliations

Affiliations

  • 1 Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 2 RIKEN-Max Planck Joint Research Division for Systems Chemical Biology, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
  • 3 Max Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
PMID: 35128925 DOI: 10.1021/acschembio.2c00028
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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