Molecular Modeling Study of c-KIT/PDGFRα Dual Inhibitors for the Treatment of Gastrointestinal Stromal Tumors.

ABSTRACT: Gastrointestinal stromal tumors (GISTs) are the most common Mesenchymal Neoplasm of the gastrointestinal tract. The tumorigenesis of GISTs has been associated with the gain-of-function mutation and abnormal activation of the stem cell factor receptor (c-KIT) and platelet-derived growth factor receptor alpha (PDGFRα) kinases. Hence, inhibitors that target c-KIT and PDGFRα could be a therapeutic option for the treatment of GISTs. The available approved c-KIT/PDGFRα inhibitors possessed low efficacy with off-target effects, which necessitated the development of potent inhibitors. We performed computational studies of 48 pyrazolopyridine derivatives that showed inhibitory activity against c-KIT and PDGFRα to study the structural properties important for inhibition of both the kinases. The deri

SUBMITTER: Keretsu S 

PROVIDER: S-EPMC7662224 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature