Targeting ROCK2 isoform with its widely used inhibitors for faster post-stroke recovery - Aix-Marseille Université Access content directly
Journal Articles Indian Journal of Biochemistry & Biophysics Year : 2021

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.
Fichier principal
Vignette du fichier
27497-465547018-3-PB.pdf (463.94 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-03283038 , version 1 (09-07-2021)

Licence

Attribution - NonCommercial - NoDerivatives

Identifiers

  • HAL Id : hal-03283038 , version 1

Cite

Sandeep Appunni, Deepika Gupta, Muni Rubens, Anjani Kumar 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⟩

Collections

INSERM UNIV-AMU
48 View
47 Download

Share

Gmail Facebook X LinkedIn More