Record Details

Targeting ROCK2 isoform with its widely used inhibitors for faster post-stroke recovery

NOPR - NISCAIR Online Periodicals Repository

View Archive Info
 
 
Field Value
 
Title Targeting ROCK2 isoform with its widely used inhibitors for faster post-stroke recovery
 
Creator Appunni, Sandeep
Gupta, Deepika
Rubens, Muni
Singh, Anjani Kumar
Swarup, Vishnu
Singh, Himanshu Narayan
 
Subject Binding affinity
Ischemic stroke
Molecular docking
Rho kinase inhibitors
 
Description 27-34
Recovery after ischemic stroke is slow and highly variable. Activated ROCK (Rho-associated coiled-coil kinase) pathway hampers recovery of impaired neurons. Though inhibiting ROCK pathway has shown therapeutic effects in vitro, the selectivity of most of the ROCK inhibitors is still not investigated. Present study aims to investigate the binding affinity in silico of nine widely used ROCK inhibitors with brain-specific ROCK2 isoform. Three-dimensional structures of ROCK2 and eight drugs were taken from Protein Data Bank and PubChem Chemical Compound Database, respectively, whereas, FSD-C10 structure was generated based on Xin et al., 2015. In docking, ROCK2 was set to be rigid and drugs were free to rotate. All simulations were carried out using AutoDock 4.2. This study demonstrated strong complexation between all ligands and ROCK2. All ROCK inhibitors, except FSD-C10, were able to bind to ROCK2 more strongly [Binding constant (Ka) between 2.6 – 36.7 × 105 M−1] than fasudil (Ka = 2.5 × 105 M−1). SLx-2119 (KD-025) had the highest binding constant (Ka = 36.7 × 105 M−1) thus succeeding as a better ROCK2 specific inhibitor. Selectivity of ROCK inhibitors (in silico) towards ROCK2 can be an indicative measure to estimate therapeutic benefits or adverse effects prior to in vitro study.
 
Date 2021-02-01T09:17:08Z
2021-02-01T09:17:08Z
2021-02
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://nopr.niscair.res.in/handle/123456789/56040
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.58(1) [February 2021]