BAY-593 (BAY593) is a potent, selective, in vivo-active YAP1/TAZ pathway inhibitor with IC50 of 9.4 nM in TEAD-luciferase assays, directly tareget PGGT1B, a subunit of the geranylgeranyltransferase-I (GGTase-I) complex.
BAY-593 potently inhibits MDA-MB-231 and HT-1080 proliferation with IC50 of 564 and 38 nM respectively.
BAY-593 effectively promoted YAP1 inactivation by translocation to the cytoplasm with an IC50 of 44 nM.
BAY-593 dose-dependently down-regulates YAP1/TAZ target genes ANKRD1, CTGF, CYR61, CDC6, and DKK1.
BAY-593 effectively inhibits GGTase-I substrates of the Rho-GTPase family in MDA-MB-231 cells, and causes YAP1/TAZ inactivation.
BAY-593 impairs cancer cell proliferation and invasion in vitro with IC50 of <1 uM against a panel of cell lines from different tumor types.
BAY-593 (5 mg/kg, BID or QD; 10 mg/kg QD, p.o.) reduces tumor growth in MDA-MB-231 human breast cancer tumors in female NMRI nu/nu mice.