Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
14 03 2019
14 03 2019
Historique:
pubmed:
12
2
2019
medline:
9
4
2020
entrez:
12
2
2019
Statut:
ppublish
Résumé
Focal adhesion tyrosine kinase (PTK2) is often overexpressed in human hepatocellular carcinoma (HCC), and several reports have linked PTK2 depletion and/or pharmacological inhibition to reduced tumorigenicity. However, the clinical relevance of targeting PTK2 still remains to be proven. Here, we present two highly selective and functional PTK2 proteolysis-targeting chimeras utilizing von Hippel-Lindau and cereblon ligands to hijack E3 ligases for PTK2 degradation. BI-3663 (cereblon-based) degrades PTK2 with a median DC
Identifiants
pubmed: 30739444
doi: 10.1021/acs.jmedchem.8b01826
doi:
Substances chimiques
Ligands
0
Protein Kinase Inhibitors
0
Recombinant Proteins
0
Focal Adhesion Kinase 1
EC 2.7.10.2
Focal Adhesion Protein-Tyrosine Kinases
EC 2.7.10.2
PTK2 protein, human
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM