American Chemical Society
jm7b01243_si_001.pdf (19.63 MB)

Structural Biology-Inspired Discovery of Novel KRAS–PDEδ Inhibitors

Download (19.63 MB)
journal contribution
posted on 2017-09-20, 00:00 authored by Yan Jiang, Chunlin Zhuang, Long Chen, Junjie Lu, Guoqiang Dong, Zhenyuan Miao, Wannian Zhang, Jian Li, Chunquan Sheng
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.