PUBLICATION
Discovery of Novel ROCK1 Inhibitors via Integrated Virtual Screening Strategy and Bioassays
- Authors
- Shen, M., Tian, S., Pan, P., Sun, H., Li, D., Li, Y., Zhou, H., Li, C., Lee, S.M., Hou, T.
- ID
- ZDB-PUB-170214-80
- Date
- 2015
- Source
- Scientific Reports 5: 16749 (Journal)
- Registered Authors
- Keywords
- High-throughput screening, Structure-based drug design
- MeSH Terms
-
- Cerebral Hemorrhage/chemically induced
- Cerebral Hemorrhage/prevention & control
- Actin Depolymerizing Factors/metabolism
- Databases, Protein
- Binding Sites
- Signal Transduction/drug effects
- Inhibitory Concentration 50
- Humans
- Protein Kinase Inhibitors/chemistry*
- Protein Kinase Inhibitors/pharmacology
- Protein Kinase Inhibitors/therapeutic use
- Animals
- Disease Models, Animal
- rho-Associated Kinases/antagonists & inhibitors*
- rho-Associated Kinases/metabolism
- Atorvastatin/pharmacology
- Phosphorylation/drug effects
- Molecular Docking Simulation
- Human Umbilical Vein Endothelial Cells
- Pyrroles/chemistry*
- Pyrroles/metabolism
- Pyrroles/therapeutic use
- Amides/chemistry
- Amides/metabolism
- Enzyme Activation/drug effects
- Structure-Activity Relationship
- Pyridines/chemistry*
- Pyridines/metabolism
- Pyridines/therapeutic use
- Protein Structure, Tertiary
- Databases, Chemical
- Zebrafish
- PubMed
- 26568382 Full text @ Sci. Rep.
Citation
Shen, M., Tian, S., Pan, P., Sun, H., Li, D., Li, Y., Zhou, H., Li, C., Lee, S.M., Hou, T. (2015) Discovery of Novel ROCK1 Inhibitors via Integrated Virtual Screening Strategy and Bioassays. Scientific Reports. 5:16749.
Abstract
Rho-associated kinases (ROCKs) have been regarded as promising drug targets for the treatment of cardiovascular diseases, nervous system diseases and cancers. In this study, a novel integrated virtual screening protocol by combining molecular docking and pharmacophore mapping based on multiple ROCK1 crystal structures was utilized to screen the ChemBridge database for discovering potential inhibitors of ROCK1. Among the 38 tested compounds, seven of them exhibited significant inhibitory activities of ROCK1 (IC50?
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping