VO-Ohpic trihydrate (VO-Ohpic) is a potent inhibitor of PTEN (phosphatase and tensin homolog) with IC50 of 35 nM.

PTEN:35 nM

VO-OHpic is a potent small-molecule compound that specifically inhibits PTEN's cellular enzymatic activity, which in turn activates downstream targets such as Akt and FoxO3a. Glucose uptake into adipocytes is dramatically enhanced upon PTEN inhibition with VO-OHpic. PTEN inhibitor accelerates wound healing in fibroblasts[1]. VO-OHpic inhibits cell viability, cell proliferation and colony formation, and induces senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells[2].

VO-Ohpic significantly inhibits tumor growth in nude mice bearing xenografts of Hep3B cells[2]. VO-Ohpic administered to C57BL6 mice 30 minutes prior to Kcl-induced asystolic cardiac arrest significantly increases survival, LVPmax and dP/dt max with continued benefit. VO-OHpic also significantly increases lactate clearance and decreases plasma glucose level[3].

VO-OHpic is dissolved in DMSO (100 μM) and diluted further to the required concentration with 1% DMSO. For inhibition studies, PTEN is preincubated with VO-OHpic at RT for 10 min before substrate is added to initialise the reaction. Background absorbance (malachite green assay) and fluorescence (OMFP assay) are determined with VO-OHpic in assay buffer and corrected in the data analysis[1].

Cell proliferation is determined by estimating the amount of bromodeoxyuridine (BrdU) incorporation into DNA by a colorimetric immunoassay. 3×103 cells are cultured in 96-well plates with varying concentrations of VO-OHpic for 72 hours. BrdU is added 24 hours before the end of the treatments. Results are expressed as the percentage inhibition of BrdU incorporation over the control.(Only for Reference)