Biological Activity
WSB1 Degrader 1 is a poten and orally active WSB1 (WD repeat and SOCS box-containing 1) degrader. WSB1 Degrader 1 has anticancer metastatic effects[1].
WSB1 Degrader 1 (compound 4; 0.25-2500 nM; 2-24 hours; H1299-WSB1 cells) treatment indues WSB1 degradation in time-dependent and dose-dependent manners[1].WSB1 Degrader 1 (compound 4) exhibits potent antimigration efficacy in both KHOS and H460 cell lines with IC50 values of 39.1 μM and 24.47 μM, respectively[1].WSB1 Degrader 1 (compound 4) significantly inhibits cancer cell migration under normoxia and hypoxia in KHOS cells. WSB1 Degrader 1 (5 μM) treatment elevates the levels of the RhoGDI2 protein in KHOS cells under hypoxia[1].The wound-healing of H1299-WSB1 cells is significantly inhibited by treating with WSB1 Degrader 1. WSB1 Degrader 1 can only block the wound-healing capability of wild-type A2780 (A2780-WT) cells but not the A2780-WSB1/KO cells[1].
WSB1 Degrader 1 (compound 4; 100 mg/kg; p.o.; daily; for 28 days) treatment can effectively inhibit the pulmonary metastasis of cancer cells[1].In rats, after 100 mg/kg oral dosing or 160 mg/kg intraperitoneal dosing of WSB1 Degrader 1 (compound 4), the two ways of administration are observed with quick absorption (Tmax), but the former dosing displayed a fast clearance (T1/2). Moreover, Cmax and AUC0-t values of WSB1 Degrader 1 in oral or intraperitoneal dosing groups showed acceptable blood exposure[1].
References
[1]. Jinxin Che, et al. Discovery of 5,6-Bis(4-methoxy-3-methylphenyl)pyridin-2-amine as a WSB1 Degrader to Inhibit Cancer Cell Metastasis. J Med Chem. 2021 Jun 1.
