ArticleNature chemical biology2022
Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S).
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 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 139 citations in OpenAlex.
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- 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
- Benzoxaboroles Are Structurally Unique Binders of Eukaryotic Translation Initiation Factor 4E.Journal of the American Chemical Society · 2026Article
- Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles.bioRxiv : the preprint server for biology · 2026Article
- Chemical adaptation: bridging synthetic chemistry with drug development.Science China. Life sciences · 2026Review
- High-throughput ligand discovery in living cells using the cellular protein stability enhancement assay.Acta pharmaceutica Sinica. B · 2026Article
- Targeting Multiple KRAS Mutations with High-Affinity Macrocyclic Inhibitors: From Discovery to Preclinical Validation.Journal of medicinal chemistry · 2026Article
- Single-Sequence Deep Learning Delivers Crystal-Quality Models of Covalent K-Ras G12 Hotspot Complexes.IUBMB life · 2026Article
- Mechanistic insights into Ras-catalyzed GTP hydrolysis: conformational dynamics, catalytic mechanisms, and emerging therapeutic strategies.Biological chemistry · 2026Review
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- A catalogue of missense and nonsense mutation abundances for the U.S. cancer patient population.medRxiv : the preprint server for health sciences · 2026Article
- Discovery of Covalent Ligands with AlphaFold3.Journal of the American Chemical Society · 2026Article
- ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC.Nature chemical biology · 2026Article
- Targeting the Reactive Proteome: Recent Advances in Activity-Based Protein Profiling and Probe Design.Biomolecules · 2025Review
- Targeting KRAS G12D: Advances in Inhibitor Design.Thoracic cancer · 2025Review
- The evolving landscape of RAS-targeted therapies.Nature cancer · 2025Article
- Proteomic Perspectives on KRAS-Driven Cancers and Emerging Therapeutic Approaches.Current oncology (Toronto, Ont.) · 2025Review
- Targeting KRASScientific reports · 2025Article
- A Modular Platform for the Optogenetic Control of Small GTPase Activity in Living Cells Reveals Long-Range RhoA Signaling.bioRxiv : the preprint server for biology · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Drugs that directly impede the function of driver oncogenes offer exceptional efficacy and a therapeutic window. The recently approved mutant selective small-molecule cysteine-reactive covalent inhibitor of the G12C mutant of K-Ras, sotorasib, provides a case in point. KRAS is the most frequently mutated proto-oncogene in human cancer, yet despite success targeting the G12C allele, targeted therapy for other hotspot mutants of KRAS has not been described. Here we report the discovery of small molecules that covalently target a G12S somatic mutation in K-Ras and suppress its oncogenic signaling. We show that these molecules are active in cells expressing K-Ras(G12S) but spare the wild-type protein. Our results provide a path to targeting a second somatic mutation in the oncogene KRAS by overcoming the weak nucleophilicity of an acquired serine residue. The chemistry we describe may serve as a basis for the selective targeting of other unactivated serines.
Indexed as
Identifiers
What OpenQuestion holds
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.