VER-49009 inhibits the intrinsic ATPase activity of recombinant yeast Hsp90 with IC50 of 167 nM, and produces antiproliferative activity in a panel of human cancer cell lines and nontumorigenic cells in vitro. VER-49009 causes induction of HSP72 and HSP27 with depletion of client proteins, including C-RAF, B-RAF, and survivin, and PRMT5, which further result in cell cycle arrest and apoptosis. VER-49009 inhibits the cell proliferation, and induces G2 phase arrest in hepatic stellate cell line CFSC cells, which may suggest a rational approach in the prevention of liver fibrosis.
In vivo
In athymic mice, VER-49009 (20 mg/kg, i.v.) shows rapid clearance with values of 0.187 L/h. In an orthotopic human ovarian carcinoma model, VER-49009 (4 mg/kg, i.p.) also induces the depletion of the sensitive HSP90 client protein ERBB2.
