Discovery of potent and selective urea-based ROCK inhibitors: Exploring the inhibitor's potency and ROCK2/PKA selectivity by 3D-QSAR, molecular docking and molecular dynamics simulations

12Citations
Citations of this article
16Readers
Mendeley users who have this article in their library.
Get full text

Abstract

An activity model and a selectivity model from 3D-QSAR studies were established by CoMFA and CoMSIA to explore the SAR. Then docking was used to study the binding modes between ligand and kinases (ROCK2 and PKA), and the molecular docking results were further validated by MD simulations. Computational results suggested that substitution containing positive charge attached to the middle phenyl ring, or electropositive group in urea linker was favored for both activity and ROCK2/PKA selectivity. Finally, three compounds were designed, and biological evaluation demonstrated that these molecular models were effective for guiding the design of potent and selective ROCK inhibitors.

Cite

CITATION STYLE

APA

Mei, D., Yin, Y., Wu, F., Cui, J., Zhou, H., Sun, G., … Feng, Y. (2015). Discovery of potent and selective urea-based ROCK inhibitors: Exploring the inhibitor’s potency and ROCK2/PKA selectivity by 3D-QSAR, molecular docking and molecular dynamics simulations. Bioorganic and Medicinal Chemistry, 23(10), 2505–2517. https://doi.org/10.1016/j.bmc.2015.03.047

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free