Novel RIPK3 inhibitors discovered through a structure-based approach exert post-ischemic neuroprotection.
Mol Divers
; 20(3): 719-28, 2016 Aug.
Article
in En
| MEDLINE
| ID: mdl-26873246
ABSTRACT
Necroptosis or programmed necrosis is evident in various neurological disorders such as ischemic stroke. Receptor interacting serine/threonine protein kinase 3 (RIPK3) is one of the crucial targets of necroptosis and inhibition of this protein exerts neuroprotection. However, knowledge regarding the three-dimensional structure and binding site information of this protein is lacking. In the present study, structure-based in silico methods were implemented to identify the key amino acids in the RIPK3 binding site that might be responsible for ligand interactions. Further, novel RIPK3 inhibitors were identified through a dual ensemble screening strategy. Three inhibitors exhibited binding to RIPK3 in micromolar concentrations and exerted post-ischemic neuroprotection in vitro.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase Inhibitors
/
Receptor-Interacting Protein Serine-Threonine Kinases
Limits:
Humans
Language:
En
Journal:
Mol Divers
Year:
2016
Document type:
Article