Necroptosis inhibitors: mechanisms of action and therapeutic potential

Apoptosis. 2024 Feb;29(1-2):22-44. doi: 10.1007/s10495-023-01905-6. Epub 2023 Nov 24.

Abstract

Necroptosis is a type of programmed cell death that is morphologically similar to necrosis. This type of cell death is involved in various pathophysiological disorders, including inflammatory, neurodegenerative, infectious, and malignant diseases. Receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) pseudokinase constitute the core components of the necroptosis signaling pathway and are considered the most promising targets for therapeutic intervention. The discovery and characterization of necroptosis inhibitors not only accelerate our understanding of the necroptosis signaling pathway but also provide important drug candidates for the treatment of necroptosis-related diseases. Here, we will review recent research progress on necroptosis inhibitors, mechanisms of action and their potential applications for disease treatment.

Keywords: Inhibitors; MLKL; Necroptosis; RIPK1; RIPK3.

Publication types

  • Review

MeSH terms

  • Apoptosis*
  • Cell Death
  • Humans
  • Necroptosis / genetics
  • Necrosis / genetics
  • Protein Kinases* / genetics
  • Protein Kinases* / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism

Substances

  • Protein Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases