Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.
Journal
Nature reviews. Drug discovery
ISSN: 1474-1784
Titre abrégé: Nat Rev Drug Discov
Pays: England
ID NLM: 101124171
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
accepted:
20
05
2020
pubmed:
17
7
2020
medline:
7
10
2020
entrez:
17
7
2020
Statut:
ppublish
Résumé
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a key mediator of cell death and inflammation. The unique hydrophobic pocket in the allosteric regulatory domain of RIPK1 has enabled the development of highly selective small-molecule inhibitors of its kinase activity, which have demonstrated safety in preclinical models and clinical trials. Potential applications of these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune, inflammatory, neurodegenerative, ischaemic and acute conditions, such as sepsis, are emerging. This article reviews RIPK1 biology and disease-associated mutations in RIPK1 signalling pathways, highlighting clinical trials of RIPK1 inhibitors and potential strategies to mitigate development challenges.
Identifiants
pubmed: 32669658
doi: 10.1038/s41573-020-0071-y
pii: 10.1038/s41573-020-0071-y
pmc: PMC7362612
doi:
Substances chimiques
Protein Kinase Inhibitors
0
RIPK1 protein, human
EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
553-571Subventions
Organisme : NIA NIH HHS
ID : R01 AG047231
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG059073
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG055521
Pays : United States
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