Targeting cancer with small-molecule pan-KRAS degraders.

doi:10.1126/science.adm8684

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Article

Targeting cancer with small-molecule pan-KRAS degraders.

Science (New York, N.Y.) - 20 Sept 2024

Popow Johannes, Farnaby William, Gollner Andreas, Kofink Christiane, Fischer Gerhard, Wurm Melanie, Zollman David, Wijaya Andre, Mischerikow Nikolai, Hasenoehrl Carina, Prokofeva Polina, Arnhof Heribert, Arce-Solano Silvia, Bell Sammy, Boeck Georg, Diers Emelyne, Frost Aileen B, Goodwin-Tindall Jake, Karolyi-Oezguer Jale, Khan Shakil, Klawatsch Theresa, Koegl Manfred, Kousek Roland, Kratochvil Barbara, Kropatsch Katrin, Lauber Arnel A, McLennan Ross, Olt Sabine, Peter Daniel, Petermann Oliver, Roessler Vanessa, Stolt-Bergner Peggy, Strack Patrick, Strauss Eva, Trainor Nicole, Vetma Vesna, Whitworth Claire, Zhong Siying, Quant Jens, Weinstabl Harald, Kuster Bernhard, Ettmayer Peter, Ciulli Alessio

Abstract excerpt

Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein are highly prevalent in cancer. However, small-molecule concepts that address oncogenic KRAS alleles remain elusive beyond replacing glycine at position 12 with cysteine (G12C), which is clinically drugged through covalent inhibitors. Guided by biophysical and structural studies of ternary complexes, we designed a heterobifunctional small...

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PMID: 39298590
DOI: 10.1126/science.adm8684

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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