Novel RIPK3 inhibitors discovered through a structure-based approach exert post-ischemic neuroprotection

S. M. Fayaz, V. S. Suvanish Kumar, Charles K. Davis, G. K. Rajanikant

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)719-728
Number of pages10
JournalMolecular Diversity
Volume20
Issue number3
DOIs
Publication statusPublished - 01-08-2016

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Information Systems
  • Molecular Biology
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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