BAY-593 free base

BAY-593 is an orally active inhibitor of geranylgeranyltransferase-I (GGTase-I) that effectively blocks the activation of Rho-GTPases, leading to the inactivation of YAP1/TAZ signaling pathways and demonstrating significant antitumor activity. In cellular assays, BAY-593 exhibits potent antiproliferative effects, with an IC₅₀ of 38.4 nM in HT-1080 fibrosarcoma cells and 564 nM in MDA-MB-231 breast cancer cells. Mechanistically, it promotes YAP1 inactivation by facilitating its cytoplasmic translocation with an IC₅₀ of 44 nM and downregulates YAP1/TAZ target genes, including ANKRD1, CTGF, CYR61, CDC6, and DKK1. In vivo studies further support its therapeutic potential, as oral administration at doses of 5 mg/kg (once or twice daily) and 10 mg/kg (once daily) significantly reduces tumor growth in MDA-MB-231 human breast cancer xenografts in female NMRI nu/nu mice