7a1w

KRASG12C GDP form in complex with Cpd3

spinqualitylabelsall models 7a1w, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.76Å Ligands: GDP, MG, PO4, QWK Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed KRAS genes belong to the most frequently mutated family of oncogenes in cancer. The G12C mutation, found in a third of lung, half of colorectal and pancreatic cancer cases, is believed to be responsible for a substantial number of cancer deaths. For 30 years, KRAS has been the subject of extensive drug-targeting efforts aimed at targeting KRAS protein itself, but also its post-translational modifications, membrane localization, protein-protein interactions and downstream signalling pathways. So far, most KRAS targeting strategies have failed, and there are no KRAS-specific drugs available. However, clinical candidates targeting the KRAS G12C protein have recently been developed. MRTX849 and recently approved Sotorasib are covalent binders targeting the mutated cysteine 12, occupying Switch II pocket.Herein, we describe two fragment screening drug discovery campaigns that led to the identification of binding pockets on the KRAS G12C surface that have not previously been described. One screen focused on non-covalent binders to KRAS G12C, the other on covalent binders. KRAS G12C fragment screening renders new binding pockets.,Mathieu M, Steier V, Fassy F, Delorme C, Papin D, Genet B, Duffieux F, Bertrand T, Delarbre L, Le-Borgne H, Parent A, Didier P, Marquette JP, Lowinski M, Houtmann J, Lamberton A, Debussche L, Alexey R Small GTPases. 2021 Sep 24:1-14. doi: 10.1080/21541248.2021.1979360. PMID:34558391 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GTPase KRas 3D structures

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