ArticleProceedings of the National Academy of Sciences of the United States of America2021
A Sos proteomimetic as a pan-Ras inhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Peptide-Based PROTACs: Transitioning from Static Paradigm to a Dynamic Landscape within Targeted Protein Degradation.Bioconjugate chemistry · 2026Review
- Cyclized Peptide Inhibitors of the Small G Protein Cdc42 Mimic Binding of Effector Proteins.Biochemistry · 2026Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Reengineering of a Proteomimetic Pan-Ras Inhibitor into a Ras Degrader.Angewandte Chemie (International ed. in English) · 2025Article
- Proteomimetic Strategy for the Modulation of Intrinsically Disordered Protein MYC.Journal of the American Chemical Society · 2025Article
- Recent Advances in Peptide Inhibitors Targeting Wild-Type Ras Protein Interactions in Cancer Therapy.International journal of molecular sciences · 2025Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma.Acta pharmacologica Sinica · 2022Article
- A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein.Nature chemical biology · 2022Article
- Covalent Proteomimetic Inhibitor of the Bacterial FtsQB Divisome Complex.Journal of the American Chemical Society · 2022Article
- Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide.Communications chemistry · 2022Article
- Trimer-to-Monomer Disruption Mechanism for a Potent, Protease-Resistant Antagonist of Tumor Necrosis Factor-α Signaling.Journal of the American Chemical Society · 2022Article
- Targeting intracellular protein-protein interactions with macrocyclic peptides.Trends in pharmacological sciences · 2022Review
- Design and Synthesis of Crosslinked Helix Dimers as Protein Tertiary Structure Mimics.Current protocols · 2022Article
- Photoaffinity labelling strategies for mapping the small molecule-protein interactome.Organic & biomolecular chemistry · 2021Review
- Discovery of a Bicyclic Peptidyl Pan-Ras Inhibitor.Journal of medicinal chemistry · 2021Article
- Protein Macrocyclization for Tertiary Structure Stabilization.Chembiochem : a European journal of chemical biology · 2021Review
- SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant Ras signaling is linked to a wide spectrum of hyperproliferative diseases, and components of the signaling pathway, including Ras, have been the subject of intense and ongoing drug discovery efforts. The cellular activity of Ras is modulated by its association with the guanine nucleotide exchange factor Son of sevenless (Sos), and the high-resolution crystal structure of the Ras-Sos complex provides a basis for the rational design of orthosteric Ras ligands. We constructed a synthetic Sos protein mimic that engages the wild-type and oncogenic forms of nucleotide-bound Ras and modulates downstream kinase signaling. The Sos mimic was designed to capture the conformation of the Sos helix-loop-helix motif that makes critical contacts with Ras in its switch region. Chemoproteomic studies illustrate that the proteomimetic engages Ras and other cellular GTPases. The synthetic proteomimetic resists proteolytic degradation and enters cells through macropinocytosis. As such, it is selectively toxic to cancer cells with up-regulated macropinocytosis, including those that feature oncogenic Ras mutations.
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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.