BAY-856 (BAY856) is a potent, selective YAP1/TAZ pathway inhibitor with IC50 of 49 nM in TEAD-luciferase assays, directly tareget PGGT1B, a subunit of the geranylgeranyltransferase-I (GGTase-I) complex.
BAY-856 potently inhibits human GGTase-I activity with biochemical IC50 of 64 nM.
BAY-856 effectively promoted YAP1 inactivation by translocation to the cytoplasm with an IC50 of 44 nM.
BAY-856 dose-dependently down-regulates YAP1/TAZ target genes ANKRD1, CTGF, CYR61, CDC6, and DKK1 with IC50 of 0.09, 0.11, 0.13, 0.14, and 0.17 μM, respectively, in MDA-MB-231 cells, with no inhibition of control gene ACTB.
BAY-856 (1 uM) effectively inhibits GGTase-I substrates of the Rho-GTPase family in MDA-MB-231 cells, and causes YAP1/TAZ inactivation.
BAY-856 impairs cancer cell proliferation and invasion in vitro with IC50 of <1 uM against a panel of cell lines from different tumor types.
BAY-856 (125 mg/kg, BID; p.o.) reduced tumor growth in MDA-MB-231 human breast cancer tumors in female NMRI nu/nu mice.