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Serine/Threonine Protein Phosphatase Inhibitors with Antitumor Activity

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Book cover Inhibitors of Protein Kinases and Protein Phosphates

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 167))

Abstract

Recent studies with fostriecin and derivatives of cantharidin suggest that the development of specific, or highly selective, inhibitors of serine/threonine protein phosphatases, notably PP2A, PP4, and PP5, may prove useful for the medical management of human cancer. This chapter will review the discovery and development of natural compounds that were originally shown to have marked antitumor activity and subsequently found to act as potent inhibitors of certain PPP-family phosphatases. The review will focus on two compounds, cantharidin and fostriecin, addressing discovery, molecular mechanisms of action, affects on cultured cell, clinical use, toxicity, plasma pharmacokinetics, and a brief review of data from a phase I human clinical trial.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of South Alabama, MSB 2362, College of Medicine, Mobile, AL, 36688, USA

    R. E. Honkanen

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  1. R. E. Honkanen
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Editors and Affiliations

  1. Dipartimento di Chimica Biologica, Università di Padova, Via Trieste 75, Padova, 35121, Italy

    Lorenzo A. Pinna

  2. MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, MSI/WTB Complex, Dow St., Dundee, DD1 5EH, Scotland, UK

    Patricia T.W. Cohen Ph.D. (Professor of Molecular Biology) (Professor of Molecular Biology)

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Honkanen, R.E. (2005). Serine/Threonine Protein Phosphatase Inhibitors with Antitumor Activity. In: Pinna, L.A., Cohen, P.T. (eds) Inhibitors of Protein Kinases and Protein Phosphates. Handbook of Experimental Pharmacology, vol 167. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26670-4_11

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