ArticleProceedings of the National Academy of Sciences of the United States of America2013
Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 96 citations in OpenAlex.
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Medicinal Phytocompounds as Potential Inhibitors of p300-HIF1α Interaction: A Structure-Based Screening and Molecular Dynamics Simulation Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Engineered coiled-coil HIF1α protein domain mimic.Biomaterials science · 2024Article
- Helical sulfonyl-γ-AApeptides for the inhibition of HIV-1 fusion and HIF-1α signaling.RSC medicinal chemistry · 2024Review
- A Lipopeptidomimetic of Transcriptional Activation Domains Selectively Disrupts the Coactivator Med25 Protein-Protein Interactions.Angewandte Chemie (International ed. in English) · 2024Article
- Bioinformatics leading to conveniently accessible, helix enforcing, bicyclic ASX motif mimics (BAMMs).Nature communications · 2024Article
- Stabilized cyclic peptides as modulators of protein-protein interactions: promising strategies and biological evaluation.RSC medicinal chemistry · 2023Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Inhibition of Hypoxia-Inducible Transcription Factor (HIF-1α) Signaling with Sulfonyl-γ-AApeptide Helices.Journal of the American Chemical Society · 2023Article
- Essential role of bromodomain proteins in renal cell carcinoma (Review).Molecular medicine reports · 2023Review
- Anchor Residues Govern Binding and Folding of an Intrinsically Disordered Domain.ACS chemical biology · 2022Article
- Understanding p300-transcription factor interactions using sequence variation and hybridization.RSC chemical biology · 2022Article
- Peptide Tethering: Pocket-Directed Fragment Screening for Peptidomimetic Inhibitor Discovery.Journal of the American Chemical Society · 2022Article
- Design of Protein Segments and Peptides for Binding to Protein Targets.Biodesign research · 2022Review
- Controlling Intramolecular Interactions in the Design of Selective, High-Affinity Ligands for the CREBBP Bromodomain.Journal of medicinal chemistry · 2021Article
- A Sos proteomimetic as a pan-Ras inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Structural optimization of reversible dibromomaleimide peptide stapling.Peptide science (Hoboken, N.J.) · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Selective blockade of gene expression by designed small molecules is a fundamental challenge at the interface of chemistry, biology, and medicine. Transcription factors have been among the most elusive targets in genetics and drug discovery, but the fields of chemical biology and genetics have evolved to a point where this task can be addressed. Herein we report the design, synthesis, and in vivo efficacy evaluation of a protein domain mimetic targeting the interaction of the p300/CBP coactivator with the transcription factor hypoxia-inducible factor-1α. Our results indicate that disrupting this interaction results in a rapid down-regulation of hypoxia-inducible genes critical for cancer progression. The observed effects were compound-specific and dose-dependent. Gene expression profiling with oligonucleotide microarrays revealed effective inhibition of hypoxia-inducible genes with relatively minimal perturbation of nontargeted signaling pathways. We observed remarkable efficacy of the compound HBS 1 in suppressing tumor growth in the fully established murine xenograft models of renal cell carcinoma of the clear cell type. Our results suggest that rationally designed synthetic mimics of protein subdomains that target the transcription factor-coactivator interfaces represent a unique approach for in vivo modulation of oncogenic signaling and arresting tumor growth.
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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.