Virtual Docking, design and in silico ADMET profiling of novel Rho-associated protein kinases-1 (ROCK1) inhibitors

Publication: 2nd International Conference on Chemo and BioInformatics, Kragujevac, September 28-29, 2023, Serbia
Software: ADMET Predictor®


Overexpression of Rho-associated protein kinases has been associated with various diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment. However, some of them have been shown to have anti-tumor potential. Them a in objective of this study was to develop novel ROCK1 inhibitors using the structure-based method, molecular docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating possible structural changes in the hinge region of studied compounds. On the other hand, the lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising approach for further structural modifications in order to design more effective ROCK1 inhibitors. All the important interactions between the developed ROCK1 inhibitors and the binding site of the enzyme were established. They also showed acceptable pharmacokinetic properties and could be further used for synthesis and evaluation by various biological assays.

By Milan Beljkas, Jelena Rebic, Milica Radan, Teodora Dikic, Slavica Oljacic, Katrina Nikolic