title: PTEN inhibitors: an evaluation of current compounds.
abstract: Small molecule inhibitors of many classes of enzymes, including phosphatases, have widespread use as experimental tools and as therapeutics. Efforts to develop inhibitors against the lipid phosphatase and tumour suppressor, PTEN, was for some time limited by concerns that their use as therapy could result in increased risk of cancer. However, the accumulation of evidence that short term PTEN inhibition may be valuable in conditions such as nerve injury has raised interest. Here we investigate the inhibition of PTEN by four available PTEN inhibitors, bpV(phen), bpV(pic), VO-OHpic and SF1670 and compared this inhibition with that of only 3 other related enzymes, the tyrosine phosphatase SHP1 and the phosphoinositide phosphatases INPP4A and INPP4B. Even with this very small number of comparators, for all compounds, inhibition of multiple enzymes was observed and with all three vanadate compounds, this was similar or more potent than the inhibition of PTEN. In particular, the bisperoxovanadate compounds were found to inhibit PTEN poorly in the presence of reducing agents including the cellular redox buffer glutathione.
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Nasmyth Building, Heriot Watt University, Edinburgh, EH14 4AS, UK; Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Spinelli
authors.affiliation: Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
authors.forename: Yvonne E
authors.initials: YE
authors.lastname: Lindsay
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Nasmyth Building, Heriot Watt University, Edinburgh, EH14 4AS, UK; Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK. Electronic address: n.r.leslie@hw.ac.uk.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Leslie
mesh_terms: D002460:Cell Line; D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014638:Vanadates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010616:Phenanthrenes; C000619508:SF1670; D025521:Tumor Suppressor Proteins; D014638:Vanadates; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Drug; Enzyme; Inhibitor; PI 3-Kinase; PTEN; Phosphatase; Phosphoinositide