Discovery of a small molecule ligand of FRS2 that inhibits invasion and tumor growth.

ABSTRACT:

Purpose

Aberrant activation of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases drives oncogenic signaling through its proximal adaptor protein FRS2. Precise disruption of this disease-causing signal transmission in metastatic cancers could stall tumor growth and progression. The purpose of this study was to identify a small molecule ligand of FRS2 to interrupt oncogenic signal transmission from activated FGFRs.

Methods

We used pharmacophore-based computational screening to identify potential small molecule ligands of the PTB domain of FRS2, which couples FRS2 to FGFRs. We confirmed PTB domain binding of molecules identified with biophysical binding assays and validated compound activity in cell-based functional assays in vitro and in an ovari

SUBMITTER: Santhana Kumar K 

PROVIDER: S-EPMC10060354 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature