title: In vivo screening of S100B inhibitors for melanoma therapy.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, The University of Maryland School of Medicine, Baltimore, MD, USA. dzimmer@som.umaryland.edu
authors.forename: Danna B
authors.initials: DB
authors.lastname: Zimmer
authors.forename: Rena G
authors.initials: RG
authors.lastname: Lapidus
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse