PTEN inhibitors: an evaluation of current compounds

Laura Spinelli, Yvonne E. Lindsay, Nicholas R. Leslie (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    47 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)102-111
    Number of pages10
    JournalAdvances in Biological Regulation
    Volume57
    DOIs
    Publication statusPublished - Jan 2015

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