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

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Title Statement Targeting ROCK2 isoform with its widely used inhibitors for faster post-stroke recovery
 
Added Entry - Uncontrolled Name Appunni, Sandeep
Gupta, Deepika
Rubens, Muni
Singh, Anjani Kumar
Swarup, Vishnu
Singh, Himanshu Narayan
 
Uncontrolled Index Term Binding affinity; Ischemic stroke; Molecular docking; Rho kinase inhibitors
 
Summary, etc. 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.
 
Publication, Distribution, Etc. Indian Journal of Biochemistry and Biophysics (IJBB)
2021-02-01 16:25:13
 
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http://op.niscair.res.in/index.php/IJBB/article/view/27497
 
Data Source Entry Indian Journal of Biochemistry and Biophysics (IJBB); IJBB Vol. 58 (1) [February 2021]
 
Language Note en
 
Nonspecific Relationship Entry http://op.niscair.res.in/index.php/IJBB/article/download/27497/465484927