From (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors
- Author(s)
- Gardner, CR; Davies, KA; Zhang, Y; Brzozowski, M; Czabotar, PE; Murphy, JM; Lessene, G;
- Details
- Publication Year 2023-02-13,Volume 66,Issue #4,Page 2361-2385
- Journal Title
- Journal of Medicinal Chemistry
- Abstract
- Necroptosis is a regulated caspase-independent form of necrotic cell death that results in an inflammatory phenotype. This process contributes profoundly to the pathophysiology of numerous neurodegenerative, cardiovascular, infectious, malignant, and inflammatory diseases. Receptor-interacting protein kinase 1 (RIPK1), RIPK3, and the mixed lineage kinase domain-like protein (MLKL) pseudokinase have been identified as the key components of necroptosis signaling and are the most promising targets for therapeutic intervention. Here, we review recent developments in the field of small-molecule inhibitors of necroptosis signaling, provide guidelines for their use as chemical probes to study necroptosis, and assess the therapeutic challenges and opportunities of such inhibitors in the treatment of a range of clinical indications.
- Publisher
- ACS
- Keywords
- Humans; Necroptosis; Necrosis; Receptor-Interacting Protein Serine-Threonine Kinases; Apoptosis
- Research Division(s)
- Chemical Biology; Inflammation; Structural Biology
- PubMed ID
- 36781172/
- Publisher's Version
- https://doi.org/10.1021/acs.jmedchem.2c01621
- Open Access at Publisher's Site
https://doi.org/ 10.1021/acs.jmedchem.2c01621- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-02-27 10:24:01
Last Modified: 2023-03-06 01:10:28