BSJ-04-146

BSJ-04-146 is a highly efficient and selective PROTAC targeting focal adhesion kinase ( FAK ) inhibitor( IC₅₀ = 26 nM). BSJ-04-146 achieves rapid and potent FAK degradation with high proteome-wide specificity in cancer cells and induces durable degradation in mice. BSJ-04-146 binds FAK and requires the ubiquitin-proteasome machinery to achieve FAK degradation. BSJ-04-146 can be used for the study of pancreatic cancer and triple-negative breast cancer ^[1]. (Pink: FAK ligand; Blue: Cereblon ligand; Black: linker).

In Vivo, BSJ-04-146 (15-50 mg/kg, i.p., once every two days (three times) or once) can induce durable and systemic FAK degradation in PATU-8988T cell xenograft mice and is well tolerated in mice^[1].

In Vitro, BSJ-04-146 (1-1000 nM, 4 h) can efficiently degrade FAK protein in PATU-8988T cells^[1]. BSJ-04-146 (100 nM, 1-24 h) can rapidly induce FAK degradation in PATU-8988T cells and simultaneously significantly reduce pAKT signaling^[1]. BSJ-04-146 (120 h) significantly inhibits the 3D spheroid viability of PATU-8988T and MDA-MB-231 cells^[1]. BSJ-04-146 (100 nM, 4-24 h) induced significant changes in 74 pY and 161 pY-IMAC phosphopeptides in PATU-8988T cells (including downregulation of FAK autophosphorylation sites); the changes persisted after 24 hours of treatment^[1].

References:
[1]. Koide E, et al. Development and Characterization of Selective FAK Inhibitors and PROTACs with In Vivo Activity. Chembiochem. 2023 Oct 4;24(19):e202300141.