NSC305787 hydrochloride ((Rac)-NSC305787 hydrochloride is a cell membrane permeable and selective and potent small molecule dual inhibitor of Cdc25 dual specificity phosphatase and EZR that displays antitumor activity in pancreatic cancer cells and inhibits Cdc25B2, Cdc25A, Cdc25B2 and Cdc25C.NSC 663284 inhibits NSD2 (IC50 of 170 nM) enzyme activity.

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

NSC305787 hydrochloride, an inhibitor of ezrin, exhibits a Kd of 5.85 μM and demonstrates antitumor activity. With IC50 values of 8.3, 9.4, 55, and 58.9 μM, NSC305787 hydrochloride inhibits PKCΙ phosphorylation of Ezrin, Moesin, Radixin, and MBP, respectively. Binding to PKCΙ with a Kd value of 172.4 μM, NSC305787 hydrochloride primarily inhibits ezrin T567 phosphorylation through its binding to ezrin, not via the inhibition of PKCΙ kinase activity. In the context of K7M2 osteosarcoma (OS) cells, NSC305787 hydrochloride (1, 10 μM) displays inhibitory activity against ezrin-mediated invasion. Furthermore, at a concentration of 10 μM, NSC305787 hydrochloride diminishes cell motility phenotypes in zebrafish and hinders OS metastatic growth in lung organ culture[2].

In a mouse model,NSC305787 hydrochloride (i.p., 0.240 mg/kg/day) effectively suppresses ezrin-dependent osteosarcoma metastatic growth in the lung[1]. Additionally, in a transgenic mouse model of osteosarcoma (Osx-Cre+p53fl/flpRBfl/fl), NSC305787 hydrochloride (i.p., 240 μg/kg) exhibits a remarkable inhibition of pulmonary metastasis. Furthermore, it demonstrates a more favorable pharmacokinetic profile compared to NSC668394 in the same mouse model[1].