ArticleBiochemistry2017
Expanding the Scope of Electrophiles Capable of Targeting K-Ras Oncogenes.
Article in Biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 92 citations in OpenAlex.
- Design, synthesis and biological evaluation of novel KRAS-G12D inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 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
- α-Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling.Nature communications · 2026Article
- Mechanistically Defined Epoxide- and Aziridine-2-carboxamide Electrophiles Enable Stereoselective Covalent Ribonucleic Acid Modulation.Journal of the American Chemical Society · 2026Article
- Mapping the SHP2 Allosteric Pocket With Target-Biased Covalent Fragments.Chembiochem : a European journal of chemical biology · 2026Article
- Synthesis and Application of Bioactive N-Functionalized Aziridines.Angewandte Chemie (International ed. in English) · 2025Review
- Denitrogenative Alkylation of K-Ras(G12D) Inhibits Oncogenic Signaling in Cancer Cells.Journal of the American Chemical Society · 2025Article
- Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations.Scientific reports · 2025Article
- RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- Recent Anti-KRASCancers · 2025Review
- Article
- Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D.Nature chemical biology · 2024Article
- Contribution of Noncovalent Recognition and Reactivity to the Optimization of Covalent Inhibitors: A Case Study on KRasACS chemical biology · 2024Article
- Synergistic anti-tumor activity, reduced pERK, and immuno-stimulatory cytokine profiles with 5-FU or ONC212 plus KRAS G12D inhibitor MRTX1133 in CRC and pancreatic cancer cells independent of G12D mutation.American journal of cancer research · 2024Article
- Crystallographic Studies of KRAS in Complex with Small Molecules and RAS-Binding Proteins.Methods in molecular biology (Clifton, N.J.) · 2024Article
- In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders.Journal of chemical information and modeling · 2023Article
- Glimmers of hope for targeting oncogenic KRAS-G12D.Cancer gene therapy · 2023Article
- The war on hTG2: warhead optimization in small molecule human tissue transglutaminase inhibitors.RSC medicinal chemistry · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
There is growing interest in reversible and irreversible covalent inhibitors that target noncatalytic amino acids in target proteins. With a goal of targeting oncogenic K-Ras variants (e.g., G12D) by expanding the types of amino acids that can be targeted by covalent inhibitors, we survey a set of electrophiles for their ability to label carboxylates. We functionalized an optimized ligand for the K-Ras switch II pocket with a set of electrophiles previously reported to react with carboxylates and characterized the ability of these compounds to react with model nucleophiles and oncogenic K-Ras proteins. Here, we report that aziridines and stabilized diazo groups preferentially react with free carboxylates over thiols. Although we did not identify a warhead that potently labels K-Ras G12D, we were able to study the interactions of many electrophiles with K-Ras, as most of the electrophiles rapidly label K-Ras G12C. We characterized the resulting complexes by crystallography, hydrogen/deuterium exchange, and differential scanning fluorimetry. Our results both demonstrate the ability of a noncatalytic cysteine to react with a diverse set of electrophiles and emphasize the importance of proper spatial arrangements between a covalent inhibitor and its intended nucleophile. We hope that these results can expand the range of electrophiles and nucleophiles of use in covalent protein modulation.
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.