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

Recovery after ischemic stroke is slow and highly variable. Activated ROCK (Rho-associated coiled-coil kinase) pathway hampers recovery of impaired neurons. Though inhibiting has shown therapeutic effects in vitro, the selectivity most inhibitors still not investigated. Present study aims to investigate binding affinity silico nine widely used with brainspecific ROCK2 isoform. Three-dimensional structures eight drugs were taken from Protein Data Bank PubChem Chemical Compound Database, respectively, whereas, FSD-C10 structure was generated based on Xin et al., 2015. In docking, set be rigid free rotate. All simulations carried out using AutoDock 4.2. This demonstrated strong complexation between all ligands ROCK2. inhibitors, except FSD-C10, able bind more strongly [Binding constant (Ka) 2.6 – 36.7 × 105 M−1] than fasudil (Ka = 2.5 M−1). SLx-2119 (KD-025) had highest M−1) thus succeeding as a better specific inhibitor. Selectivity (in silico) towards can an indicative measure estimate benefits or adverse prior vitro study.