ArticleProceedings of the National Academy of Sciences of the United States of America2023
Exploiting the intrinsic misfolding propensity of the KRAS oncoprotein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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
7 citing papers in PubMed, 9 citations in OpenAlex.
- Heterobifunctional proteomimetic polymers for targeted degradation of MYC and KRAS.Nature communications · 2026Article
- Co-translational protein aggregation and ribosome stalling as a broad-spectrum antibacterial mechanism.Nature communications · 2025Article
- AggNet: Advancing protein aggregation analysis through deep learning and protein language model.Protein science : a publication of the Protein Society · 2025Article
- Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.Nature chemical engineering · 2024Article
- CORDAX web server: an online platform for the prediction and 3D visualization of aggregation motifs in protein sequences.Bioinformatics (Oxford, England) · 2024Article
- KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance.Current oncology (Toronto, Ont.) · 2024Review
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutant KRAS is a major driver of oncogenesis in a multitude of cancers but remains a challenging target for classical small molecule drugs, motivating the exploration of alternative approaches. Here, we show that aggregation-prone regions (APRs) in the primary sequence of the oncoprotein constitute intrinsic vulnerabilities that can be exploited to misfold KRAS into protein aggregates. Conveniently, this propensity that is present in wild-type KRAS is increased in the common oncogenic mutations at positions 12 and 13. We show that synthetic peptides (Pept-ins™) derived from two distinct KRAS APRs could induce the misfolding and subsequent loss of function of oncogenic KRAS, both of recombinantly produced protein in solution, during cell-free translation and in cancer cells. The Pept-ins exerted antiproliferative activity against a range of mutant KRAS cell lines and abrogated tumor growth in a syngeneic lung adenocarcinoma mouse model driven by mutant KRAS G12V. These findings provide proof-of-concept that the intrinsic misfolding propensity of the KRAS oncoprotein can be exploited to cause its functional inactivation.
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.