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Journal of Chemical Biology

, Volume 3, Issue 4, pp 157–163 | Cite as

Characterisation of the PTEN inhibitor VO-OHpic

  • Lok Hang MakEmail author
  • Ramón Vilar
  • Rudiger Woscholski
Short Communication

Abstract

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a phosphatidylinositol triphosphate 3-phosphatase that counteracts phosphoinositide 3-kinases and has subsequently been implied as a valuable drug target for diabetes and cancer. Recently, we demonstrated that VO-OHpic is an extremely potent inhibitor of PTEN with nanomolar affinity in vitro and in vivo. Given the importance of this inhibitor for future drug design and development, its mode of action needed to be elucidated. It was discovered that inhibition of recombinant PTEN by VO-OHpic is fully reversible. Both K m and V max are affected by VO-OHpic, demonstrating a noncompetitive inhibition of PTEN. The inhibition constants K ic and K iu were determined to be 27 ± 6 and 45 ± 11 nM, respectively. Using the artificial phosphatase substrate 3-O-methylfluorescein phosphate (OMFP) or the physiological substrate phosphatidylinositol 3,4,5-triphosphate (PIP3) comparable parameters were obtained suggesting that OMFP is a suitable substrate for PTEN inhibition studies and PTEN drug screening.

Keywords

PTEN VO-OHpic OMFP PIP3 

Notes

Acknowledgments

This work was supported by the Leverhulme Trust project grant (project reference, F/07 058/AO).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Lok Hang Mak
    • 1
    Email author
  • Ramón Vilar
    • 2
  • Rudiger Woscholski
    • 1
  1. 1.Division of Cell and Molecular BiologyImperial College LondonLondonUK
  2. 2.Department of ChemistryImperial College LondonLondonUK

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