タイトル | An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations. |
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ジャーナル・号・ページ | Sci Transl Med, Vol. 16, Page eadi0979-eadi0979, Year 2024 |
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掲載日 | 2021年10月1日 (構造データの登録日) |
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著者 | Westberg, M. / Su, Y. / Zou, X. / Huang, P. / Rustagi, A. / Garhyan, J. / Patel, P.B. / Fernandez, D. / Wu, Y. / Hao, C. ...Westberg, M. / Su, Y. / Zou, X. / Huang, P. / Rustagi, A. / Garhyan, J. / Patel, P.B. / Fernandez, D. / Wu, Y. / Hao, C. / Lo, C.W. / Karim, M. / Ning, L. / Beck, A. / Saenkham-Huntsinger, P. / Tat, V. / Drelich, A. / Peng, B.H. / Einav, S. / Tseng, C.K. / Blish, C. / Lin, M.Z. |
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リンク | Sci Transl Med / PubMed:38478629 |
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手法 | X線回折 |
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解像度 | 1.7 - 2 Å |
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構造データ | PDB-7set: SARS-CoV-2 Main Protease (Mpro) in Complex with ML1000 手法: X-RAY DIFFRACTION / 解像度: 1.7 Å PDB-7sf1: SARS-CoV-2 Main Protease (Mpro) in Complex with ML1001 手法: X-RAY DIFFRACTION / 解像度: 1.85 Å PDB-7sf3: SARS-CoV-2 Main Protease (Mpro) in Complex with ML1006m 手法: X-RAY DIFFRACTION / 解像度: 1.75 Å PDB-7u92: SARS-CoV-2 Main Protease (Mpro) in Complex with ML1006a 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å PDB-7uug: SARS-CoV-2 Main Protease S144A (Mpro S144A) in Complex with ML1006a 手法: X-RAY DIFFRACTION / 解像度: 2 Å PDB-7uup: SARS-CoV-2 Main Protease S144A (Mpro S144A) in Complex with Nirmatrelvir (PF-07321332) 手法: X-RAY DIFFRACTION / 解像度: 2 Å PDB-8ezv: SARS-CoV-2 Main Protease (Mpro) in Complex with ML2006a 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å PDB-8ezz: SARS-CoV-2 Main Protease (Mpro) in Complex with ML2006a2 手法: X-RAY DIFFRACTION / 解像度: 1.85 Å PDB-8f02: SARS-CoV-2 Main Protease (Mpro) in Complex with ML2006a4 手法: X-RAY DIFFRACTION / 解像度: 2 Å PDB-8f2c: SARS-CoV-2 Main Protease (Mpro) in Complex with ML3006a 手法: X-RAY DIFFRACTION / 解像度: 1.95 Å PDB-8f2d: SARS-CoV-2 Main Protease (Mpro) in Complex with ML4006a 手法: X-RAY DIFFRACTION / 解像度: 1.95 Å |
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化合物 | ChemComp-I70: (1R,2S,5S)-N-{(2S,3R)-4-amino-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-3-[N-(tert-butylcarbamoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-8ZI: (1R,2S,5S)-N-{(2S,3R)-4-amino-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-3-[N-(3,3-dimethylbutanoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-90H: (1R,2S,5S)-N-{(2S,3R)-3-hydroxy-4-(methylamino)-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-M0C: (1R,2S,5S)-N-{(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-4WI: (1R,2S,5S)-N-{(1E,2S)-1-imino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide / 薬剤, 抗ウイルス剤, プロテアーゼ阻害剤*YM
ChemComp-X6O: (1R,2S,5S)-N-{(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-X70: (1R,2S,5S)-N-{(2S,3R)-4-(3,3-difluoroazetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-X6T: (1R,2S,5S)-N-{(2S,3R)-4-(3,3-dimethylazetidin-1-yl)-3-hydroxy-4-oxo-1-[(3S)-2-oxopiperidin-3-yl]butan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-X9Z: (1R,2S,5S)-N-[(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-(2-oxopyrrolidin-1-yl)butan-2-yl]-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
ChemComp-XA8: (1R,2S,5S)-N-[(2S,3R)-4-(azetidin-1-yl)-3-hydroxy-4-oxo-1-(2-oxopiperidin-1-yl)butan-2-yl]-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide
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由来 | - severe acute respiratory syndrome coronavirus 2 (ウイルス)
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キーワード | VIRAL PROTEIN / SARSCoV2 / SARS-CoV-2 / coronavirus / Main Protease / Protease / Mpro / 3C-like proteinase / CL3pro / Inhibitor / Complex / Covalent / Adduct / ML1000 / Ketoamide / Peptidomimetic / ML1001 / ML1006m / ML1006a / Azetidine / S144A / mutant / resistance / Nirmatrelvir / PF-07321332 / Nitrile / M2006a / M2006a2 / M2006a4 / M3006a / M4006a |
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