R428 (Bemcentinib, BGB324) is potent, selective and orally bioavailable inhibitor of Axl kinase with IC50 of 14 nM.
R428 inhibits phosphorylation of Akt (Ser473) and Axl (Tyr821) in cell-based activity assays.
R428 exhibits>100-fold selectivity for Axl versus Abl and 50- and >100-fold selectivity over TAM family kinases Mer and Tyro3, respectively, in cells.
R428 is >100-fold selective for Axl over insulin receptor,EGFR, HER2, and PDGFRβ and kinases of other subfamilies.
R428 (0-3 uM) dose dependently suppresses invasion of both human MDA-MB-231 and murine 4T1 breast cancer cell lines.
R428 (125 mg/kg, BID) suppresses breast cancer metastasis in MDA-MB-231 xenograft and orthotopic 4T1 models.
R428 suppresses angiogenesis in vivo and modulates expression of surrogate markers in tumor tissue.
