タイトル | Targeting cancer with small molecule pan-KRAS degraders |
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ジャーナル・号・ページ | Biorxiv, Year 2023 |
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掲載日 | 2023年10月14日 (構造データの登録日) |
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著者 | Popow J / Farnaby W / Gollner A / Kofink C / Fischer G / Wurm M / Zollman D / Wijaya A / Mischerikow N / Hasenoehrl C ...Popow J / Farnaby W / Gollner A / Kofink C / Fischer G / Wurm M / Zollman D / Wijaya A / Mischerikow N / Hasenoehrl C / Prokofeva P / Arnhof H / Arce-Solano S / Bell S / Boeck G / Diers E / Frost A / Goodwin-Tindall J / Karolyi-Oezguer J / Khan S / Klawatsch T / Koegl M / Kousek R / Kratochvil B / Kropatsch K / Lauber A / McLennan R / Olt S / Peter D / Petermann O / Roessler V / Stolt-Bergner P / Strack P / Strauss E / Trainor N / Vetma V / Whitworth C / Zhong S / Quant J / Weinstabl H / Kuster B / Ettmayer P / Ciulli A |
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リンク | Biorxiv / PubMedで検索 |
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手法 | EM (単粒子) / X線回折 |
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解像度 | 1.56 - 3.5 Å |
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構造データ | EMDB-18657, PDB-8qu8: PROTAC-mediated complex of KRAS with VHL/Elongin-B/Elongin-C/Cullin-2/Rbx1 手法: EM (単粒子) / 解像度: 3.5 Å PDB-8qug: KRAS-G12C in Complex with Compound 1 手法: X-RAY DIFFRACTION / 解像度: 1.56 Å PDB-8qvu: Crystal Structure of ligand ACBI3 in complex with KRAS G12D C118S GDP and pVHL:ElonginC:ElonginB complex 手法: X-RAY DIFFRACTION / 解像度: 2.24 Å PDB-8qw6: Crystal Structure of compound 3 in complex with KRAS G12V C118S GDP and pVHL:ElonginC:ElonginB 手法: X-RAY DIFFRACTION / 解像度: 2.2 Å PDB-8qw7: Crystal Structure of compound 4 in complex with KRAS G12V C118S GDP and pVHL:ElonginC:ElonginB 手法: X-RAY DIFFRACTION / 解像度: 2.36 Å |
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化合物 | ChemComp-WYL: (2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]butoxy]-1,2,3-triazol-1-yl]-3-methyl-butanoyl]-N-[(1R)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-2-oxidanyl-ethyl]-4-oxidanyl-pyrrolidine-2-carboxamide
ChemComp-WYU: (4S)-2-azanyl-4-methyl-4-[3-[2-[(2S)-2-methyl-1,4-diazepan-1-yl]pyrimidin-4-yl]-1,2,4-oxadiazol-5-yl]-6,7-dihydro-5H-1-benzothiophene-3-carbonitrile
ChemComp-X4R: (2S,4R)-1-[(2S)-2-[6-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]hexanoylamino]-3,3-dimethyl-butanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide
ChemComp-X53: (2S,4R)-1-[(2R)-2-[3-[4-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-methyl-6,7-dihydro-5H-1-benzothiophen-4-yl]-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]-3-methyl-1,4-diazepan-1-yl]butoxy]-1,2-oxazol-5-yl]-3-methyl-butanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide
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由来 | - homo sapiens (ヒト)
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キーワード | TRANSFERASE / TARGETED PROTEIN DEGRADATION / PROTAC / GTPASE / KRAS / cancer / GENE REGULATION / Ternary Complex / Degrader / E3 ligase / Ligase / ONCOPROTEIN / oncology |
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