R428

R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective) . (In Vitro) :Bemcentinib (R428) (2μM) significantly interferes with mechanisms of migration and invasion of Axlpos melanoma cells at levels comparable to Axl knockdown. Bemcentinib (R428) synergizes with CDDP to enhance suppression of liver micrometastasis. Bemcentinib (R428) (50 nM-1μM) causes a concentration-dependent inhibition of preadipocyte differentiation into mature adipocytes, as evidenced by reduced lipid uptake. (In Vivo) :Bemcentinib (R428) (125 mg/kg, p.o.) significantly blocks MDA-MB-231-luc-D3H2LN metastases development in two independent mouse models of breast cancer dissemination, suppresses both tumor angiogenesis and vascular endothelial growth factor (VEGF) -induced corneal neovascularization in vivo. Bemcentinib (R428) (75 mg/kg/day, 25 mg/kg twice daily, p.o.) makes mice keep on a high-fat diet resulted in significantly reduced weight gain and subcutaneous and gonadal fat mass.