NSC305787 HYDROCHLORIDE

Kd: 5.85 μM (ezrin)
IC50: 8.3 μM (ezrin)

NSC305787 hydrochloride is an inhibitor of ezrin with a K _d of 5.85 μM, and has antitumor activity. NSC305787 inhibits PKCΙ phosphorylation of Ezrin, Moesin, Radixin, MBP, with IC ₅₀ s of 8.3, 9.4, 55, 58.9 μM, respectively. NSC305787 binds to PKCΙ with a K _d value of 172.4 μM, and inhibits ezrin T567 phosphorylation primarily via its binding to ezrin and not through inhibition of PKCΙ kinase activity. NSC305787 (1, 10 μM) shows inhibitory activity against ezrin-mediated invasion of K7M2 osteosarcoma (OS) cells. Moreover, NSC305787 (10 μM) reduces cell motility phenotypes in zebrafish and blocks OS metastatic growth in lung organ culture.

NSC305787 (0.240 mg/kg/day, i.p.) suppresses ezrin-dependent osteosarcoma metastatic growth in mouse lung. NSC305787 (240 μg/kg, i.p.) dramatically inhibits pulmonary metastasis in a transgenic mouse model of osteosarcoma (Osx-Cre ⁺ p53 ^fl/fl pRB ^fl/fl ) and shows a more favorable pharmacokinetic profile compared with NSC668394 in the mouse model.