Ontology highlight
ABSTRACT:
SUBMITTER: Zhao H
PROVIDER: S-EPMC4025670 | biostudies-literature | 2012 Oct
REPOSITORIES: biostudies-literature
ACS medicinal chemistry letters 20120823 10
We have discovered a novel chemical class of inhibitors of the EphB4 tyrosine kinase by fragment-based high-throughput docking followed by explicit solvent molecular dynamics simulations for assessment of the binding mode. The synthesis of a single derivative (compound 7) of the hit identified in silico has resulted in an improvement of the inhibitory potency in an enzymatic assay from 8.4 μM to 160 nM and a ligand efficiency of 0.39 kcal/mol per non-hydrogen atom. Such remarkable improvement in ...[more]