ArticleACS omega2019
Discovery of High-Affinity Noncovalent Allosteric KRAS Inhibitors That Disrupt Effector Binding.
Article in ACS omega, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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.
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.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Design of new drugs for medullary thyroid carcinoma.Frontiers in oncology · 2022Pooled it
- RinPy, a Python Package for Residue Interaction Network Model to Analyze Protein Structures and Predict Ligand Binding Sites.Journal of chemical information and modeling · 2026Article
- Synthesis and Biochemical Characterization of Investigational Pyrazolopyrimidine-Based Allosteric KRAS Modulators.ACS medicinal chemistry letters · 2026Article
- Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C.Journal of medicinal chemistry · 2026Article
- Advances in biomarkers of resistance to KRAS mutation-targeted inhibitors.Discover oncology · 2025Review
- Evolution of computational techniques against various KRAS mutants in search for therapeutic drugs: a review article.Cancer chemotherapy and pharmacology · 2025Review
- In Silico Identification of Putative Allosteric Pockets and Inhibitors for the KRASG13D-SOS1 Complex in Cancer Therapy.International journal of molecular sciences · 2025Article
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Identification and Analysis of Anticancer Therapeutic Targets from the Polysaccharide Krestin (PSK) and Polysaccharopeptide (PSP) Using Inverse Docking.Molecules (Basel, Switzerland) · 2024Article
- Review
- Insights into direct KRAS inhibition strategies for cancer treatment.Future medicinal chemistry · 2024Review
- Discovery of Hit Compounds Targeting the P4 Allosteric Site of K-RAS, Identified through Ensemble-Based Virtual Screening.Journal of chemical information and modeling · 2023Article
- Kinetic and thermodynamic allostery in the Ras protein family.Biophysical journal · 2023Article
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Article
- In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders.Journal of chemical information and modeling · 2023Article
- Eliminating oncogenic RAS: back to the future at the drawing board.Biochemical Society transactions · 2023Article
- Molecular Research in Pancreatic Cancer: Small Molecule Inhibitors, Their Mechanistic Pathways and Beyond.Current issues in molecular biology · 2023Review
- Identification of bioactive compounds fromIn silico pharmacology · 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
11 authors at 3 institutions in 1 country.
Funding
Abstract
Approximately 15% of all human tumors harbor mutant KRAS, a membrane-associated small GTPase and notorious oncogene. Mutations that render KRAS constitutively active will lead to uncontrolled cell growth and cancer. However, despite aggressive efforts in recent years, there are no drugs on the market that directly target KRAS and inhibit its aberrant functions. In the current work, we combined structure-based design with a battery of cell and biophysical assays to discover a novel pyrazolopyrimidine-based allosteric KRAS inhibitor that binds to activated KRAS with sub-micromolar affinity and disrupts effector binding, thereby inhibiting KRAS signaling and cancer cell growth. These results show that pyrazolopyrimidine-based compounds may represent a first-in-class allosteric noncovalent inhibitors of KRAS. Moreover, by studying two of its analogues, we identified key chemical features of the compound that interact with a set of specific residues at the switch regions of KRAS and play critical roles for its high-affinity binding and unique mode of action, thus providing a blueprint for future optimization efforts.
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.