Determine Active and Inactive Pyridine-based SHP۲ Inhibitors

SHP۲ affects the transduction of multiple signaling pathways which is associated with breast, liver and gastric cancers. In this work, stepwise MLR, PLS and PCA-DA models were developed for Pyridine derivatives as selective SHP۲ inhibitors. The PCA-DA classification models with accuracy of ۹۱% indicates that the molecular descriptors of RDF۰۶۵m, RDF۰۲۵v and G۲u can categorize active/inactive inhibitors. Moreover, the molecular docking analysis showed that the Arg۱۱۱, Glu۲۴۹, Glu۲۵۰, Pro۴۹۱ and Thr۲۱۹ residues have significant roles in the activities of the inhibitors. The results can be used as valuable tools to design more effective new SHP۲ inhibitors for cancer treatment.

Keywords:

Molecular Docking , PCA-DA , QSAR , Tyrosine-protein phosphatase.