Identification of a small molecule that enhances ferroptosis via inhibition of FSP1.
Identification of a small molecule that enhances ferroptosis via inhibition of FSP1.
复制标题
鉴定通过抑制 FSP1 增强铁死亡的小分子。
DOI：
10.1021/acschembio.2c00028
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发表时间：
2022
影响因子：
4
通讯作者：
Osada H.
中科院分区：
文献类型：
--
作者：
Yoshioka H;Kawamura T;Muroi M;Kondoh Y;Honda K;Kawatani M;Aono H;Waldmann H;Watanabe N;Osada H.
谷胱甘肽过氧化物酶4（GPX 4）是一种细胞内酶，其氧化谷胱甘肽同时减少脂质过氧化物，并且是癌症治疗的有希望的靶点。迄今为止，已经报道了几种GPX4抑制剂对癌细胞表现出细胞毒性。然而，一些癌细胞对已知的GPX4抑制剂不太敏感。本研究旨在探索与GPX4抑制剂显示协同作用的化合物。我们筛选了一个化学库，并确定了一种名为NPD 4928的化合物，其细胞毒性在GPX 4抑制剂的存在下增强。此外，我们确定了铁凋亡抑制蛋白1作为其靶蛋白。结果表明，NPD 4928增强了各种癌细胞对GPX 4抑制剂的敏感性，表明该组合可能具有通过诱导铁凋亡的治疗潜力。
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.