Necroptosis has been recently confirmed as a non-apoptotic form of programmed cell death. Discovery of novel chemical entities, capable of inducing necroptosis of cancer cells, is likely to act as an alternative strategy for dealing with drug resistance clinically. In this study, the identification of a novel Pleuromutilin derivative (compound 38) is presented, capable of significantly increasing the cellular level of ROS and inducing melanoma cancer cell death via necroptosis. Furthermore, compound 38 noticeably ablated various cancer stem cells and inhibited the growth of melanoma cancer cells both in vitro and in vivo. Moreover, 38 exhibited low toxicity in animal models and excellent PK properties, which is currently being verified as a potential anticancer drug candidate.

中文翻译：

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截短侧耳素衍生的新型抗癌干细胞化合物可诱导黑色素瘤细胞坏死

坏死性凋亡最近已被证实为程序性细胞死亡的非凋亡形式。发现能够诱导癌细胞坏死性凋亡的新化学实体可能会作为临床上应对耐药性的替代策略。在这项研究中，提出了一种新型截短侧耳素衍生物（化合物38）的鉴定，该衍生物能够显着增加 ROS 的细胞水平并通过坏死性凋亡诱导黑色素瘤癌细胞死亡。此外，化合物38在体外和体内都显着消融了各种癌症干细胞并抑制了黑色素瘤癌细胞的生长。此外，38在动物模型中表现出低毒性和优异的 PK 特性，目前正在被验证为潜在的抗癌候选药物。