VO-Ohpic (trihydrate)

VO-Ohpic trihydrate is a highly potent inhibitor of PTEN with an IC₅₀ of 46±10 nM. IC50 & Target:IC50: 46±10 nM (PTEN)^[1] In Vitro: VO-OHpic with two OHpic ligands and an oxo ligand is a sterically demanding molecule, and one will therefore expect that binds substrate will affect the subsequent binding of the inhibitor due to steric hindrance. VO-OHpic significantly inhibits PTEN activity in low nanomolar concentrations (IC₅₀, 46±10 nM), which is in agreement with the previously determined potency (IC₅₀, 35±2 nM) in a PIP₃-based assay. The inhibition constants K_ic and K_iu are determined to be 27±6 and 45±11 nM, respectively^[1]. VO-OHpic is an encouragingly specific and potent PTEN inhibitor. VO-OHpic is the most potent inhibitor (IC₅₀=35 nM) of the PTEN lipid phosphatase activity^[2]. In Vivo: PTEN is inhibited in mice by intra-peritoneal injection of VO-OHpic (10 μg/kg) 30 min before ischemia and then exposed them to 30 min of ischemia and 120 min of reperfusion. At the end of the experiment, myocardial infarct size is measured by triphenyltetrazolium chloride (TTC). Myocardial infarct size is significantly decreased in VO-treated mice (25±6 vs. 56±5 %, n=7, P<0.01). There is no difference in the area at risk between these two groups (46±3 vs. 57±3 %, n=7, P>0.05)^[3].