Due to the vital role in many cell regulatory processes, such as cell cycle control, survival and apoptosis, as
well as growth and neurotransmitter signaling, Src homology 2 (SH2) domain-containing phosphatase 2(Shp2) has attracted
considerable attention for developing drugs to treat cancers. In this study, by means of the powerful “core hopping”
technique, a novel class of inhibitors was discovered based on the compound II-B08. It was observed by molecular
dynamics simulations that these novel inhibitors not only possessed the same function as II-B08 did in inhibiting Shp2,
but also had stronger binding to the receptor. It was further validated by the outcomes of their ADME (absorption, distribution,
metabolism, and excretion) predictions that the new inhibitors hold high potential to become promising drug candidates
for developing novel and powerful drugs for anticancer. Subsequently, in vitro evaluation of promising hits revealed
a novel and selective inhibitor of Shp2.
Keywords: ADME, core hopping, drug design, molecular dynamics, Shp2, selective inhibitors.
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