Dovitinib Ameliorates Inflammation-Related Diseases by Inhibiting Necroptosis and Ferroptosis

作者：Yingying Lin, Jianting Feng, Mingyuan Zhao, Libo Zhang, Yan Li, Xuan Chen, Chuibing Lin, Junxiong Lin, Qiaofa Lin, Jing Li, Lanqin Wu, Lisheng Li · 发表于：ACS Chemical Biology · 年份：2025 · DOI：10.1021/acschembio.5c00327 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Cancer, Lipids, and Metabolism

Abnormal and dysregulated cell death plays important roles in organ injury. Necroptosis and ferroptosis are two distinct types of regulated cell death that can trigger inflammation and are involved in organ injury. The inhibition of necroptosis and ferroptosis is proposed to be beneficial for treating multiple pathological conditions. To find out necroptosis and ferroptosis inhibitors, we used a small-molecule compound library for screening and identified a clinically advanced compound, Dovitinib (Dov), as a potent dual inhibitor of necroptosis and ferroptosis. Dov inhibited tumor necrosis factor (TNF)-induced necroptosis by regulating receptor-interacting protein kinase 1 (RIPK1) and alleviated TNF-mediated systemic inflammatory response syndrome. Additionally, Dov inhibited ferroptosis by regulating the NRF2/HMOX1 axis and lipid peroxidation and protected against concanavalin A-induced acute liver injury. Thus, our work revealed that Dov is a dual inhibitor of necroptosis and ferroptosis and provides a potential therapeutic drug or combination approach for treating necroptosis- and ferroptosis-related diseases.