ArticleInternational journal of molecular sciences2022
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 17 citations in OpenAlex.
- Integrating computational chemistry and machine learning to predict KRAS mutation-induced resistance.bioRxiv : the preprint server for biology · 2026Article
- Theoretical study of KRAS G12C secondary mutations influencing inhibitor resistance.Biophysics and physicobiology · 2026Article
- Molecular screening of natural compounds targeting KRAS(G12C): a multi-parametric strategy against acute lymphoblastic leukemia.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Advances in biomarkers of resistance to KRAS mutation-targeted inhibitors.Discover oncology · 2025Review
- Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations.Scientific reports · 2025Article
- The complex journey of targeting RAS in oncology.BMC cancer · 2025Review
- Evolution of computational techniques against various KRAS mutants in search for therapeutic drugs: a review article.Cancer chemotherapy and pharmacology · 2025Review
- Assessing the mechanism of fast-cycling cancer-associated mutations of Rac1 small Rho GTPase.Protein science : a publication of the Protein Society · 2024Article
- A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation.Cancer gene therapy · 2024Article
- A Nexus between Genetic and Non-Genetic Mechanisms Guides KRAS Inhibitor Resistance in Lung Cancer.Biomolecules · 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 1 country.
Funding
Abstract
Kirsten rat sarcoma viral oncogene homolog (KRAS) is a small GTPase protein which plays an important role in the treatment of KRAS mutant cancers. The FDA-approved AMG510 and MRTX849 (phase III clinical trials) are two potent KRASG12C-selective inhibitors that target KRAS G12C. However, the drug resistance caused by the second-site mutation in KRAS has emerged, and the mechanisms of drug resistance at atom level are still unclear. To clarify the mechanisms of drug resistance, we conducted long time molecular dynamics simulations (75 μs in total) to study the structural and energetic features of KRAS G12C and its four drug resistant variants to inhibitors. The combined binding free energy calculation and protein-ligand interaction fingerprint revealed that these second-site mutations indeed caused KRAS to produce different degrees of resistance to AMG510 and MRTX849. Furthermore, Markov State Models and 2D-free energy landscapes analysis revealed the difference in conformational changes of mutated KRAS bound with and without inhibitors. Furthermore, the comparative analysis of these systems showed that there were differences in their allosteric signal pathways. These findings provide the molecular mechanism of drug resistance, which helps to guide novel KRAS G12C inhibitor design to overcome drug resistance.
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.