Fluorescence based live cell imaging identifies exon 14 skipped hepatocyte growth factor receptor (MET) degraders.

ABSTRACT: Despite ongoing efforts to employ structure-based methods to discover targeted protein degraders (TPD), the prevailing strategy continues to be the synthesis of a focused set of heterobifunctional compounds and screening them for target protein degradation. Here we used a fluorescence based live cell imaging screen to identify degraders that target exon 14 skipped hepatocyte growth factor receptor (MET). MET is a known oncogenic driver. MET exon 14 skipping mutations (METex14Δ) are found in lung cancers and result in the loss of a degron that is required for E3-ligase recognition and subsequent ubiquitination, prolonging the half-life and oncogenicity of MET. Since proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that promote target degradation by the proteosome, w

SUBMITTER: Mallareddy JR 

PROVIDER: S-EPMC11967169 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature