bi-3663

Description: BI-3663 is a novel, potent, functional and highly selective PTK2/FAK degrader based on PROTAC (proteolysis-targeting chimeras) technology, utilizing VHL (von Hippel-Lindau) and cereblon ligands to hijack E3 ligases for PTK2 degradation. BI-3663 inhibits PTK2 with an IC50 of 18 nM. 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. BI-3663 (cereblon-based) degrades PTK2 with a median DC50 of 30 nM to > 80% across a panel of 11 HCC cell lines. Despite effective PTK2 degradation, these compounds did not phenocopy the reported antiproliferative effects of PTK2 depletion in any of the cell lines tested.

References: J Med Chem. 2019 Mar 14; 62(5):2508-2520.