The vanadium complex VO-OHpic is a potent, reversible, allosteric inhibitor of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) which hydrolyzes the 3-phosphate from phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3, formed from PI(4,5)P2 though phosphorylation by PI 3-kinase, activates numerous signaling pathways resulting in cell proliferation, growth, survival, glucose transport and protein synthesis. VO-OHpic is reported to be selective for PTEN (IC50~35 nM) compared with other cysteine-based phosphatases (PTPbeta, SAC, MTM, & SopB, IC50>4 µM). Treatment of insulin-stimulated NIH 3T3 and L1 fibroblasts caused an increase in Akt-phosphorylation indicating inhibition of PTEN in vivo.
