NSC305787 is an ezrin inhibitor with antitumor activity, inhibits PKCΙ-induced ezrin phosphorylation, reduces β2AR expression in the cell membrane, and induces intracellular vesicular or punctate expression of ezrin and β2AR, and can be used to study pancreatic cancer.

Ezrin:5.85 μM (kd), Ezrin:8.3 μM, Moesin:9.4 μM, MBP:58.9 μM, Radixin:55 μM, PKCΙ:172.4 μM (Kd)

NSC305787 is a small molecule inhibitor that specifically targets ezrin with a binding dissociation constant (Kd) of 5.85 μM and shows significant anti-tumor effects. The compound exhibited different inhibitory activities by inhibiting the phosphorylation of ezrin, moesin, radixin, and MBP by PKCI with IC50 values of 8.3 μM, 9.4 μM, 55 μM, and 58.9 μM, respectively.Although NSC305787 was also bound to PKCI (Kd=172.4 μM), it inhibited ezrin mainly through direct binding to ezrin. Although NSC305787 also binds to PKCI (Kd=172.4 μM), it mainly inhibits the phosphorylation of ezrin T567 by directly binding to ezrin, rather than by blocking PKCI kinase activity.
In cellular assays, NSC305787 significantly inhibited the ezrin-mediated invasion of K7M2 osteosarcoma cells at concentrations of 1 μM and 10 μM. In addition, NSC305787 was able to reduce the cell motility phenotype in zebrafish at a concentration of 10 μM and effectively blocked the metastatic growth of osteosarcoma in lung organ culture. [1]

In in vivo experiments, NSC305787 (0.240 mg/kg/day, intraperitoneal injection) significantly inhibited the growth of ezrin-dependent osteosarcoma metastases in the lungs of mice. [1]
In a transgenic osteosarcoma mouse model (Osx-Cre+p53fl/flpRBfl/fl), NSC305787 (240 μg/kg, intraperitoneal injection) also significantly inhibited lung metastasis while demonstrating superior pharmacokinetic properties to NSC305787. [2]