Structural Biology-Inspired Discovery of Novel KRAS–PDEδ Inhibitors

Structural
biology is a powerful tool for investigating the stereospecific
interactions between a protein and its ligand. Herein, an unprecedented
chiral binding pattern was observed for inhibitors of KRAS–PDEδ
interactions. Virtual screening and X-ray crystallography studies
revealed that two enantiomers of a racemic inhibitor could bind at
different sites. Fragment-based drug design was used to identify highly
potent PDEδ inhibitors that can be used as promising lead compounds
for target validation and antitumor drug development.