| References: |
Y15 is a novel small molecule FAK phosphorylation inhibitor; specifically block phosphorylation of Y397-FAK and total phosphorylation of FAK.
in vitro: directly inhibited FAK autophosphorylation in a dose- and time-dependent manner. Furthermore, Y15 increased pancreatic cancer cell detachment and inhibited cell adhesion in a dose-dependent manner. Inhibition of FAK pathway using Y15 significantly decreased cell survival, adhesion, and promoted apoptosis. Y15 significantly decreased viability and clonogenicity in a dose-dependent manner, increased detachment in a dose- and time-dependent manner, caused apoptosis, and inhibited cell invasion in both cell lines. In addition, Y15 treatment decreased autophosphorylation of FAK in a dose-dependent manner and changed cell morphology by causing cell rounding in DBTRG and U87 cells.
in vivo: Y15 effectively caused human pancreatic tumor regression in vivo, when administered alone and its effects were synergistic with gemcitabine chemotherapy. The combination of Y15 treatment and IGF-1R knockdown also showed significant antitumor effect in vivo. Y15 was administered in an orthotopic glioma model, leading to an increase in mouse survival. |
