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

Fayaz, S M and Kumar, Suvanish V S and Davis, Charles K and Rajanikant, G K (2016) Novel RIPK3 inhibitors discovered through a structure-based approach exert post-ischemic neuroprotection. Molecular Diversity, 20 (3). pp. 719-728. ISSN 1381-1991

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Official URL: http://link.springer.com/article/10.1007/s11030-01...

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 postischemic neuroprotection in vitro

Item Type: Article
Uncontrolled Keywords: Necroptosis · Ischemic stroke · Dual ensemble screening (DES) · Post-ischemic neuroprotection
Subjects: Engineering > MIT Manipal > Biotechnology
Depositing User: MIT Library
Date Deposited: 07 Nov 2016 10:51
Last Modified: 07 Nov 2016 10:51
URI: http://eprints.manipal.edu/id/eprint/147482

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