Investigating natural compounds against oncogenic RET tyrosine kinase using pharmacoinformatic approaches for cancer therapeutics.

ABSTRACT: Rearranged during transfection (RET) tyrosine kinase is a transmembrane receptor tyrosine kinase regulating vital aspects of cellular proliferation, differentiation, and survival. An outstanding challenge in designing protein kinase inhibitors is due to the development of drug resistance. The "gain of function" mutations in the RET gate-keeper residue, Val804, confers resistance to the majority of known RET inhibitors, including vandetanib. To curtail this resistance, researchers developed selpercatinib (LOXO-292) against the RET gate-keeper mutant forms - V804M and V804L. In the present in silico investigation, a receptor-ligand pharmacophore model was generated to identify small molecule inhibitors effective for wild-type (WT) as well as mutant RET kinase variants. The generated m

SUBMITTER: Parate S 

PROVIDER: S-EPMC8978841 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature