ArticleJournal of the American Chemical Society2013
In vivo activation of the p53 tumor suppressor pathway by an engineered cyclotide.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 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.
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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
86 citing papers in PubMed, 229 citations in OpenAlex.
- Computational screening of Viola odorata cyclotides identifies Phyb C as potential PD-1 inhibitor for cancer immunotherapy.Molecular diversity · 2026Article
- Design of a cyclic peptide targeting intracellular Staphylococcus aureus.Molecular biomedicine · 2026Article
- Tangled Tail of Mechanically Interlocked Peptides.Journal of the American Chemical Society · 2026Review
- Natural Products Beyond Inhibition: A Mechanistic Framework Spanning Pockets, Interfaces, and Kinetic Barriers.Molecules (Basel, Switzerland) · 2026Review
- A Comprehensive Review on the Anticancer Activity of Plant Peptides and Their Mechanisms of Action.Foods (Basel, Switzerland) · 2026Review
- Advances in cyclotide research: bioactivity to cyclotide-based therapeutics.Molecular diversity · 2025Review
- Unlocking the Therapeutic Potential of Cyclic Peptide-Based Nanocarriers for Enhanced Colon Cancer Treatment.The protein journal · 2025Review
- The Potential of Peptide-Based Inhibitors in Disrupting Protein-Protein Interactions for Targeted Cancer Therapy.International journal of molecular sciences · 2025Review
- Plant Defense Peptides: Exploring the Structure-Function Correlation for Potential Applications in Drug Design and Therapeutics.ACS omega · 2025Review
- Small and Versatile Cyclotides as Anti-infective Agents.ACS infectious diseases · 2025Review
- Effective Strategies in Designing Chitosan-hyaluronic Acid Nanocarriers: From Synthesis to Drug Delivery Towards Chemotherapy.Current drug delivery · 2025Review
- Molecular Chimera in Cancer Drug Discovery: Beyond Antibody Therapy, Designing Grafted Stable Peptides Targeting Cancer.International journal of peptide research and therapeutics · 2025Review
- Chemical synthesis of grafted cyclotides using a "plug and play" approach.RSC chemical biology · 2024Article
- Discovery and Characterization of MaK: A Novel Knottin Antimicrobial Peptide fromInternational journal of molecular sciences · 2023Article
- Resistance is futile: targeting multidrug-resistant bacteria withRSC chemical biology · 2023Review
- Lipidation of a bioactive cyclotide-based CXCR4 antagonist greatly improves its pharmacokinetic profile in vivo.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Pyrrolysine-Inspired in Cellulo Synthesis of an Unnatural Amino Acid for Facile Macrocyclization of Proteins.Journal of the American Chemical Society · 2023Article
- Native and Engineered Cyclic Disulfide-Rich Peptides as Drug Leads.Molecules (Basel, Switzerland) · 2023Review
- Selection and evolution of disulfide-rich peptidesChemical science · 2023Article
- Molecular Peptide Grafting as a Tool to Create Novel Protein Therapeutics.Molecules (Basel, Switzerland) · 2023Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The overexpression of Hdm2 and HdmX is a common mechanism used by many tumor cells to inactive the p53 tumor suppressor pathway promoting cell survival. Targeting Hdm2 and HdmX has emerged as a validated therapeutic strategy for treating cancers with wild-type p53. Small linear peptides mimicking the N-terminal fragment of p53 have been shown to be potent Hdm2/HdmX antagonists. The potential therapeutic use of these peptides, however, is limited by their poor stability and bioavailability. Here, we report the engineering of the cyclotide MCoTI-I to efficiently antagonize intracellular p53 degradation. The resulting cyclotide MCo-PMI was able to bind with low nanomolar affinity to both Hdm2 and HdmX, showed high stability in human serum, and was cytotoxic to wild-type p53 cancer cell lines by activating the p53 tumor suppressor pathway both in vitro and in vivo. These features make the cyclotide MCoTI-I an optimal scaffold for targeting intracellular 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.