细胞死亡对于几乎所有多细胞生物的发育和稳态调节至关重要。此外，细胞死亡的失调会导致多种疾病状态。历史上，认为凋亡是主要的调控性细胞死亡途径，而坏死则被认为是一种非调控性细胞死亡形式。然而，近几十年的研究揭示了几种与退行性疾病、炎症和癌症相关的调控性坏死形式。对这些非凋亡细胞死亡途径的不断深入了解，为治疗靶向开辟了新的途径。在这里，我们描述了坏死程序化细胞死亡、焦亡、帕尔坦纳托斯、缺铁性死亡、缺铜性死亡、溶酶锌死亡和二硫键死亡的调控途径。我们讨论了对这些途径的小分子抑制剂及未来药物研发的前景。综上所述，这些途径所监视的复杂机制提供了控制非凋亡性细胞死亡的治疗策略。© 2023. Springer Nature Limited.

Cell death is critical for the development and homeostasis of almost all multicellular organisms. Moreover, its dysregulation leads to diverse disease states. Historically, apoptosis was thought to be the major regulated cell death pathway, whereas necrosis was considered to be an unregulated form of cell death. However, research in recent decades has uncovered several forms of regulated necrosis that are implicated in degenerative diseases, inflammatory conditions and cancer. The growing insight into these regulated, non-apoptotic cell death pathways has opened new avenues for therapeutic targeting. Here, we describe the regulatory pathways of necroptosis, pyroptosis, parthanatos, ferroptosis, cuproptosis, lysozincrosis and disulfidptosis. We discuss small-molecule inhibitors of the pathways and prospects for future drug discovery. Together, the complex mechanisms governing these pathways offer strategies to develop therapeutics that control non-apoptotic cell death.© 2023. Springer Nature Limited.