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In Vivo Screening of S100B Inhibitors for Melanoma Therapy

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Calcium-Binding Proteins and RAGE

Part of the book series: Methods in Molecular Biology ((MIMB,volume 963))

Abstract

S100 proteins are markers for numerous cancers, and in many cases high S100 protein levels are a prognostic indicator for poor survival. One such case is S100B, which is overproduced in a very large percentage of malignant melanoma cases. Elevated S100B protein was more recently validated to have causative effects towards cancer progression via down-regulating the tumor suppressor protein, p53. Towards eliminating this problem in melanoma, targeting S100B with small molecule inhibitors was initiated. This work relies on numerous chemical biology technologies including structural biology, computer-aided drug design, compound screening, and medicinal chemistry approaches. Another important component of drug development is the ability to test compounds and various molecular scaffolds for their efficacy in vivo. This chapter briefly describes the development of S100B inhibitors, termed SBiXs, for melanoma therapy with a focus on the inclusion of in vivo screening at an early stage in the drug discovery process.

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Acknowledgments

These studies were supported by NIH grant CA107331 (DJW) and the Center for Biomolecular Therapeutics (CBT), The University of Maryland School of Medicine, and the Institute for Bioscience and Biotechnology Research (IBBR).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, The University of Maryland School of Medicine, Baltimore, MD, USA

    Danna B. Zimmer

  2. Center for Biomolecular Therapeutics, Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    Rena G. Lapidus

  3. Center for Biomolecular Therapeutics, The University of Maryland, School of Medicine, The University of Maryland, Baltimore, MD, USA

    David J. Weber

Authors
  1. Danna B. Zimmer
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  2. Rena G. Lapidus
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  3. David J. Weber
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Correspondence to Danna B. Zimmer or David J. Weber .

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Editors and Affiliations

  1. Div of Clinical Chem & Biochem, Department of Pediatrics, University of Zürich, Steinwiesstrasse 75, Zürich, 8032, Switzerland

    Claus W. Heizmann

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Zimmer, D.B., Lapidus, R.G., Weber, D.J. (2013). In Vivo Screening of S100B Inhibitors for Melanoma Therapy. In: Heizmann, C. (eds) Calcium-Binding Proteins and RAGE. Methods in Molecular Biology, vol 963. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-230-8_18

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  • DOI: https://doi.org/10.1007/978-1-62703-230-8_18

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-229-2

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