Inhibitors Targeting RIPK1/RIPK3: Old and New Drugs.
Trends Pharmacol Sci
; 41(3): 209-224, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32035657
ABSTRACT
The scaffolding function of receptor-interacting protein kinase 1 (RIPK1) regulates prosurvival signaling and inflammatory gene expression, while its kinase activity mediates both apoptosis and necroptosis; the latter involving RIPK3 kinase activity. The mutual transition between the scaffold and kinase functions of RIPK1 is regulated by (de)ubiquitylation and (de)phosphorylation. RIPK1-mediated cell death leads to disruption of epithelial barriers and/or release of damage-associated molecular patterns (DAMPs), cytokines, and chemokines, propagating inflammatory and degenerative diseases. Many drug development programs have pursued targeting RIPK1, and to a lesser extent RIPK3 kinase activity. In this review, we classify existing and novel small-molecule drugs based on their pharmacodynamic (PD) type I, II, and III binding mode. Finally, we discuss their applicability and therapeutic potential in inflammatory and degenerative experimental disease models.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Proteína Serina-Treonina Quinases de Interação com Receptores
Limite:
Humans
Idioma:
En
Revista:
Trends Pharmacol Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Bélgica