Calcium-Binding Proteins and RAGE pp 303-317

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

In Vivo Screening of S100B Inhibitors for Melanoma Therapy



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.

Key words

In vivo screening Preclinical testing Intratumoral delivery Systemic delivery Pharmacokinetics Pharmacodynamics Maximum tolerated dose Therapeutic window Genetically modified mouse models S100 proteins EF-hand 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Center for Biomolecular TherapeuticsThe University of Maryland School of MedicineBaltimoreUSA
  2. 2.Center for Biomolecular Therapeutics, Marlene and Stewart Greenebaum Cancer CenterUniversity of MarylandBaltimoreUSA
  3. 3.Center for Biomolecular TherapeuticsThe University of Maryland, School of Medicine, The University of MarylandBaltimoreUSA

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