ArticleNature chemical biology2022
KRAS is vulnerable to reversible switch-II pocket engagement in cells.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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Who cites it
66 citing papers in PubMed, 99 citations in OpenAlex.
- Discovery of a novel and potent KRASJournal of enzyme inhibition and medicinal chemistry · 2026Article
- Identification and validation of natural product-based KRASMolecular diversity · 2026Article
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Expanding Addressable KRAS Mutations through the Structure- and Property-Based Design of Dual-State (GDP/GTP), Reversible Pan-KRAS Inhibitors.Journal of medicinal chemistry · 2026Article
- Evolution of KRAS molecular glues: from allele-selective to Pan-RAS and protein-protein interaction modulators.Acta pharmacologica Sinica · 2026Review
- The AUTACE That Degrades KRAS and Engages CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Posttranslational modifications remodel proteome-wide ligandability.Nature chemical biology · 2026Article
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- Advances in BRET probes for intracellular target engagement studies.Nature chemical biology · 2026Review
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- An evolutionarily conserved salt bridge stabilizes the active site for GTP hydrolysis in Rho GTPases.The Journal of biological chemistry · 2026Article
- Cyclized Peptide Inhibitors of the Small G Protein Cdc42 Mimic Binding of Effector Proteins.Biochemistry · 2026Article
- Immune checkpoint inhibitor-based combinatory and alternative strategies for immune treatment of lung cancers.Frontiers in immunology · 2026Review
- Unbiased RNA Degrader Identification Uncovers an LC3B-Recruiting Chimera forJournal of the American Chemical Society · 2025Article
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Broad-Spectrum RAS Inhibition in Pancreatic Ductal Adenocarcinoma: Mechanistic Advances and Therapeutic Promise.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A nucleotide-independent, pan-RAS-targeted DARPin elicits anti-tumor activity in a multimodal manner.Molecular oncology · 2025Article
- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Current small-molecule inhibitors of KRAS(G12C) bind irreversibly in the switch-II pocket (SII-P), exploiting the strong nucleophilicity of the acquired cysteine as well as the preponderance of the GDP-bound form of this mutant. Nevertheless, many oncogenic KRAS mutants lack these two features, and it remains unknown whether targeting the SII-P is a practical therapeutic approach for KRAS mutants beyond G12C. Here we use NMR spectroscopy and a cellular KRAS engagement assay to address this question by examining a collection of SII-P ligands from the literature and from our own laboratory. We show that the SII-Ps of many KRAS hotspot (G12, G13, Q61) mutants are accessible using noncovalent ligands, and that this accessibility is not necessarily coupled to the GDP state of KRAS. The results we describe here emphasize the SII-P as a privileged drug-binding site on KRAS and unveil new therapeutic opportunities in RAS-driven cancer.
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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.