The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Breaking down KRAS: small-molecule degraders for cancer therapy
Open accessAbstract
In their recently published study in Science , Popow and colleagues developed a proteolysis-targeting chimera (PROTAC) for the in vivo degradation of several oncogenic KRAS variants. 1 Leveraging detailed biophysical analyses and crystal structures of ternary complexes of candidate ligands for KRAS and the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, they designed a small molecule capable of potently and selectively targeting 13 of the 17 most common KRAS mutants.
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PROTAC technologies are designed to induce selective degradation of KRAS proteins through recruitment of E3 ubiquitin ligases and subsequent proteasomal destruction.
“PROTAC (proteolysis-targeting chimera) technologies are designed to induce selective degradation of KRAS proteins through recruitment of E3 ubiquitin ligases and subsequent proteasomal destruction [61,62,63,64].”
From Precision Targeting of KRAS-Mutant Cancers: Beyond G12C Toward G12D and Pan-RAS Therapeutic Strategies (2026) · cites this paper as [64]
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Acquired Resistance to KRAS G12C Inhibition in Cancer
Awad, M. M., Liu, S., Rybkin, I. I., Arbour, K. C., Dilly, J., Zhu, V. W., Johnson, M. L., Heist, R. S., Patil, T., Riely, G. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105281 · Cited by 1,247
Targeting cancer with small-molecule pan-KRAS degraders
Popow, J., Farnaby, W., Gollner, A., Kofink, C., Fischer, G., Wurm, M., Zollman, D., Wijaya, A., Mischerikow, N., Hasenoehrl, C., et al. (2024) · Science · doi:10.1126/science.adm8684 · Cited by 198
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Research works printed but not linked: 3
- Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A. & Shokat, K. M. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 503, 548–551 (2013). · DOI · Paper page
- Kim, D. et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature 619, 160–166 (2023). · DOI · Paper page
- Chirnomas, D., Hornberger, K. R. & Crews, C. M. Protein degraders enter the clinic - a new approach to cancer therapy. Nat. Rev. Clin. Oncol. 20, 265–278 (2023). · DOI · Paper page
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Kano, Y. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27135796
Metadata
- Authors
- Kos, T., & Saur, D.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Saur, Dieter
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2025-03-14
- Volume
- 10
- Issue
- 1
- Pages
- 86-86
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC11906874
- OpenAlex
- W4408394991
- Cited by
- 15
- References
- 2
- Citations by year
- 2026: 9 · 2025: 6
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Krebshilfe (70115743)
- Wilhelm Sander-Stiftung (2020.174.1 and 2017.091.2)
- Deutsche Forschungsgemeinschaft (DFG SA 1374/8-1, Project-ID 515991405, DFG SA 1374/7-1, Project-ID 515571394, DFG SA 1374/6-1, Project ID 458890590, DFG SA 1374/4-3, Project ID 219542602)
- German Cancer Consortium (DKTK) and German Cancer Research Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- KRAS, PROTACs, small-molecule degraders, protein degradation, cancer therapy, ternary complex crystal structure, ligand design
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