ArticleBiochemistry2014
Covalent small molecule inhibitors of Ca(2+)-bound S100B.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Hierarchical AF2RAVE for Multiconformation Virtual Screening Targeting S100 CaJournal of chemical theory and computation · 2025Article
- Novel piperazine-1,2,3-triazole leads for the potential treatment of pancreatic cancer.RSC medicinal chemistry · 2023Article
- Binding and Functional Folding (BFF): A Physiological Framework for Studying Biomolecular Interactions and Allostery.Journal of molecular biology · 2022Review
- Reactivity and binding mode of disulfiram, its metabolites, and derivatives in SARS-CoV-2 PLJournal of molecular modeling · 2022Article
- S100 Proteins as Novel Therapeutic Targets in Psoriasis and Other Autoimmune Diseases.Molecules (Basel, Switzerland) · 2022Review
- Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma.Journal of cellular and molecular medicine · 2021Article
- Computational Design of Macrocyclic Binders of S100B(ββ): Novel Peptide Theranostics.Molecules (Basel, Switzerland) · 2021Article
- Specificity of Molecular Fragments Binding to S100B versus S100A1 as Identified by NMR and Site Identification by Ligand Competitive Saturation (SILCS).Molecules (Basel, Switzerland) · 2021Article
- Proteomimetic surface fragments distinguish targets by function.Chemical science · 2020Article
- The Trp triad within the V-domain of the receptor for advanced glycation end products modulates folding, stability and ligand binding.Bioscience reports · 2020Article
- S100 proteins as therapeutic targets.Biophysical reviews · 2018Review
- Structural Basis for S100B Interaction with its Target Proteins.Journal of molecular and genetic medicine : an international journal of biomedical research · 2018Article
- Solving the crystal structure of human calcium-free S100Z: the siege and conquer of one of the last S100 family strongholds.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
- X-ray crystal structure of human calcium-bound S100A1.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Nanosurveyor: a framework for real-time data processing.Advanced structural and chemical imaging · 2017Article
- Binding of transition metals to S100 proteins.Science China. Life sciences · 2016Review
- Novel protein-inhibitor interactions in site 3 of Ca(2+)-bound S100B as discovered by X-ray crystallography.Acta crystallographica. Section D, Structural biology · 2016Article
- Fluorescence polarization assays in high-throughput screening and drug discovery: a review.Methods and applications in fluorescence · 2016Article
- Small Molecule Inhibitors of Ca(2+)-S100B Reveal Two Protein Conformations.Journal of medicinal chemistry · 2016Article
- Structural Basis of Ribosomal S6 Kinase 1 (RSK1) Inhibition by S100B Protein: MODULATION OF THE EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK) SIGNALING CASCADE IN A CALCIUM-DEPENDENT WAY.The Journal of biological chemistry · 2016Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Elevated levels of the tumor marker S100B are observed in malignant melanoma, and this EF-hand-containing protein was shown to directly bind wild-type (wt) p53 in a Ca(2+)-dependent manner, dissociate the p53 tetramer, and inhibit its tumor suppression functions. Likewise, inhibiting S100B with small interfering RNA (siRNA(S100B)) is sufficient to restore wild-type p53 levels and its downstream gene products and induce the arrest of cell growth and UV-dependent apoptosis in malignant melanoma. Therefore, it is a goal to develop S100B inhibitors (SBiXs) that inhibit the S100B-p53 complex and restore active p53 in this deadly cancer. Using a structure-activity relationship by nuclear magnetic resonance approach (SAR by NMR), three persistent binding pockets are found on S100B, termed sites 1-3. While inhibitors that simultaneously bind sites 2 and 3 are in place, no molecules that simultaneously bind all three persistent sites are available. For this purpose, Cys84 was used in this study as a potential means to bridge sites 1 and 2 because it is located in a small crevice between these two deeper pockets on the protein. Using a fluorescence polarization competition assay, several Cys84-modified S100B complexes were identified and examined further. For five such SBiX-S100B complexes, crystallographic structures confirmed their covalent binding to Cys84 near site 2 and thus present straightforward chemical biology strategies for bridging sites 1 and 3. Importantly, one such compound, SC1982, showed an S100B-dependent death response in assays with WM115 malignant melanoma cells, so it will be particularly useful for the design of SBiX molecules with improved affinity and specificity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.