ArticleChemistry & biology2013
Structure-based design of covalent Siah inhibitors.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed.
- A Fragment-Based Electrophile-First Approach to Target Histidine with Aryl-Fluorosulfates: Application to hMcl-1.Journal of medicinal chemistry · 2025Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.Journal of the American Chemical Society · 2025Article
- Discovering covalent cyclic peptide inhibitors of peptidyl arginine deiminase 4 (PADI4) using mRNA-display with a genetically encoded electrophilic warhead.Communications chemistry · 2024Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.bioRxiv : the preprint server for biology · 2024Article
- Biospecific Chemistry for Covalent Linking of Biomacromolecules.Chemical reviews · 2024Review
- SIAH2 suppresses c-JUN pathway by promoting the polyubiquitination and degradation of HBx in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2024Article
- TP-LMMSG: a peptide prediction graph neural network incorporating flexible amino acid property representation.Briefings in bioinformatics · 2024Article
- Advancing protein therapeutics through proximity-induced chemistry.Cell chemical biology · 2024Review
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- Characterization of a Potent and Orally Bioavailable Lys-Covalent Inhibitor of Apoptosis Protein (IAP) Antagonist.Journal of medicinal chemistry · 2023Article
- Peptide-based covalent inhibitors of protein-protein interactions.Journal of peptide science : an official publication of the European Peptide Society · 2023Review
- Zooming into the structure-function of RING finger proteins for anti-cancer therapeutic applications.American journal of cancer research · 2023Review
- Advanced approaches of developing targeted covalent drugs.RSC medicinal chemistry · 2022Review
- Rapid Covalent Labeling of Membrane Proteins on Living Cells Using a Nanobody-Epitope Tag Pair.Bioconjugate chemistry · 2022Article
- Covalent Proteomimetic Inhibitor of the Bacterial FtsQB Divisome Complex.Journal of the American Chemical Society · 2022Article
- P-TEFb is degraded by Siah1/2 in quiescent cells.Nucleic acids research · 2022Article
- Design, Synthesis, and Structural Characterization of Lysine Covalent BH3 Peptides Targeting Mcl-1.Journal of medicinal chemistry · 2021Article
- E3 ubiquitin ligase-mediated regulation of vertebrate ocular development; new insights into the function of SIAH enzymes.Biochemical Society transactions · 2021Review
- Regulation of the SIAH2-HIF-1 Axis by Protein Kinases and Its Implication in Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Siah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy.Nature communications · 2020Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The E3 ubiquitin ligase Siah regulates key cellular events that are central to cancer development and progression. A promising route to Siah inhibition is disrupting its interactions with adaptor proteins. However, typical of protein-protein interactions, traditional unbiased approaches to ligand discovery did not produce viable hits against this target, despite considerable effort and a multitude of approaches. Ultimately, a rational structure-based design strategy was successful for the identification of Siah inhibitors in which peptide binding drives specific covalent bond formation with the target. X-ray crystallography, mass spectrometry, and functional data demonstrate that these peptide mimetics are efficient covalent inhibitors of Siah and antagonize Siah-dependent regulation of Erk and Hif signaling in the cell. The proposed strategy may result useful as a general approach to the design of peptide-based inhibitors of other protein-protein interactions.
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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.