Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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 (K a) between 2.6-36.7 × 10 5 M −1 ] than fasudil (Ka = 2.5 × 10 5 M −1). SLx-2119 (KD-025) had the highest binding constant (K a = 36.7 × 10 5 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.
Document type :
Journal articles
Complete list of metadata

https://hal-amu.archives-ouvertes.fr/hal-03283038
Contributor : Lionel Spinelli Connect in order to contact the contributor
Submitted on : Friday, July 9, 2021 - 3:55:53 PM
Last modification on : Tuesday, August 31, 2021 - 4:22:39 PM
Long-term archiving on: : Sunday, October 10, 2021 - 7:44:46 PM

File

27497-465547018-3-PB.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

  • HAL Id : hal-03283038, version 1

Collections

Citation

Sandeep Appunni, Deepika Gupta, Muni Rubens, Anjani Singh, Vishnu Swarup, et al.. Targeting ROCK2 isoform with its widely used inhibitors for faster post-stroke recovery. Indian Journal of Biochemistry & Biophysics, 2021, 58, pp.27-34. ⟨hal-03283038⟩

Share

Metrics

Record views

12

Files downloads

15