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PTEN (Phosphatase and tensin homologue deleted on chromosome 10), a phosphoinositide 3-phosphatase, is an important regulator of insulin-dependent signaling. The loss or impairment of PTEN results in an antidiabetic impact, which led to the suggestion that PTEN could be an important target for drugs against type II diabetes. PTEN has a much wider active site cleft enabling it to bind the PtdIns(3,4,5)P3 substrate. a highly potent and specific inhibitor of PTEN that increases cellular PtdIns(3,4,5)P3 levels, phosphorylation of Akt, and glucose uptake in adipocytes at nanomolar concentrations.

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VO-Ohpic trihydrate


VO-Ohpic trihydrate (VO-Ohpic) is a potent, selective and reversible PTEN inhibitor with IC50 of 35 nM in vitro; specifically inhibits PTEN’s cellular enzymatic activity, which in turn activates downstream targets such as Akt and FoxO3a, inhibits cell viability, cell proliferation and colony formation, and induces senescence-associated β-galactosidase activity in Hep3B cells (low PTEN expression); increases cellular PIP3 levels, phosphorylation of Akt, and glucose uptake in adipocytes at nanomolar concentrations; decreases left ventricular systolic pressure and heart rate before ischemia in mice.

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