Advances in RIPK1 kinase inhibitors

Programmed necrosis is a new modulated cell death mode with necrotizing morphological characteristics. Receptor interacting protein 1 (RIPK1) is a critical mediator of the programmed necrosis pathway that is involved in stroke, myocardial infarction, fatal systemic inflammatory response syndrome, Alzheimer's disease, and malignancy. At present, the reported inhibitors are divided into four categories. The first category is the type I ATP-competitive kinase inhibitors that targets the area occupied by the ATP adenylate ring; The second category is type II ATP competitive kinase inhibitors targeting the DLG-out conformation of RIPK1; The third category is type III kinase inhibitors that compete for binding to allosteric sites near ATP pockets; The last category is others. This paper reviews the structure, biological function, and recent research progress of receptor interaction protein-1 kinase inhibitors.

Automated summary

Programmed necrosis is a novel cell death mode characterized by necrotic morphological features. RIPK1 plays a vital role in the programmed necrosis pathway and is involved in various diseases. Inhibitors targeting RIPK1 can be categorized into four types based on their mechanisms of action. This review summarizes the structure, biological function, and recent progress of receptor interaction protein-1 kinase inhibitors.