7N5Y
| Fragment-Based Drug Design of a Novel, Covalent Bruton's Tyrosine Kinase Inhibitor | 分子名称: | 5-(1-{[(3S)-1-propanoylpyrrolidin-3-yl]oxy}isoquinolin-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one, DIMETHYL SULFOXIDE, IMIDAZOLE, ... | 著者 | Dougan, D.R, Lawson, J.D. | 登録日 | 2021-06-07 | 公開日 | 2021-09-08 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (1.85 Å) | 主引用文献 | Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 ( S )-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3 H -1,2,4-triazol-3-one, by Fragment-Based Drug Design. J.Med.Chem., 64, 2021
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8UF2
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8UH0
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8UC9
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8T5G
| SOS2 co-crystal structure with fragment bound (compound 12) | 分子名称: | DIMETHYL SULFOXIDE, SULFATE ION, Son of sevenless homolog 2, ... | 著者 | Gunn, R.J, Lawson, J.D, Ivetac, A, Ulaganathan, T, Coulombe, R, Fethiere, J. | 登録日 | 2023-06-13 | 公開日 | 2024-01-10 | 最終更新日 | 2024-01-24 | 実験手法 | X-RAY DIFFRACTION (1.92 Å) | 主引用文献 | Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography. J.Med.Chem., 67, 2024
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8T5M
| SOS2 crystal structure with fragment bound (compound 14) | 分子名称: | 1,2-ETHANEDIOL, 4-[(1R,2S)-1-hydroxy-2-{[2-(4-hydroxyphenyl)ethyl]amino}propyl]phenol, SULFATE ION, ... | 著者 | Gunn, R.J, Lawson, J.D, Ivetac, A, Ulaganathan, T, Coulombe, R, Fethiere, J. | 登録日 | 2023-06-14 | 公開日 | 2024-01-10 | 最終更新日 | 2024-01-24 | 実験手法 | X-RAY DIFFRACTION (1.79 Å) | 主引用文献 | Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography. J.Med.Chem., 67, 2024
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8T5R
| SOS2 crystal structure with fragment bound (compound 13) | 分子名称: | 4-(aminomethyl)benzene-1-sulfonamide, SULFATE ION, Son of sevenless homolog 2 | 著者 | Gunn, R.J, Lawson, J.D, Ivetac, A, Ulaganathan, T, Coulombe, R, Fethiere, J. | 登録日 | 2023-06-14 | 公開日 | 2024-01-10 | 最終更新日 | 2024-01-24 | 実験手法 | X-RAY DIFFRACTION (2.12 Å) | 主引用文献 | Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography. J.Med.Chem., 67, 2024
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7UKS
| Crystal structure of SOS1 with phthalazine inhibitor bound (compound 15) | 分子名称: | 4-methyl-N-{(1R)-1-[2-methyl-3-(trifluoromethyl)phenyl]ethyl}-7-(piperazin-1-yl)phthalazin-1-amine, Son of sevenless homolog 1 | 著者 | Gunn, R.J, Lawson, J.D, Ketcham, J.M, Marx, M.A. | 登録日 | 2022-04-01 | 公開日 | 2022-07-27 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.29 Å) | 主引用文献 | Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction. J.Med.Chem., 65, 2022
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7UKR
| Crystal Structure of SOS1 with MRTX0902, a Potent and Selective Inhibitor of the SOS1:KRAS Protein-Protein Interaction | 分子名称: | 2-methyl-3-[(1R)-1-{[4-methyl-7-(morpholin-4-yl)pyrido[3,4-d]pyridazin-1-yl]amino}ethyl]benzonitrile, Son of sevenless homolog 1 | 著者 | Gunn, R.J, Lawson, J.D, Ketcham, J.M, Marx, M.A. | 登録日 | 2022-04-01 | 公開日 | 2022-07-27 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.5 Å) | 主引用文献 | Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction. J.Med.Chem., 65, 2022
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7UYF
| Human PRMT5:MEP50 structure with Fragment 4 and MTA Bound | 分子名称: | 4-methyl-1,5-naphthyridin-2-amine, 5'-DEOXY-5'-METHYLTHIOADENOSINE, CHLORIDE ION, ... | 著者 | Gunn, R.J, Lawson, J.D, Smith, C.R. | 登録日 | 2022-05-06 | 公開日 | 2022-10-05 | 最終更新日 | 2024-05-22 | 実験手法 | X-RAY DIFFRACTION (2.82 Å) | 主引用文献 | Fragment optimization and elaboration strategies - the discovery of two lead series of PRMT5/MTA inhibitors from five fragment hits. Rsc Med Chem, 13, 2022
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5TC0
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5TD2
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5UAB
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5UAD
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5USQ
| ALK-5 kinase inhibitor complex | 分子名称: | N-[2-(5-chloro-2-fluorophenyl)pyridin-4-yl]-2-[(piperidin-4-yl)methyl]-2H-pyrazolo[4,3-b]pyridin-7-amine, TGF-beta receptor type-1 | 著者 | Dougan, D.R, Lawson, J.D. | 登録日 | 2017-02-13 | 公開日 | 2017-04-12 | 最終更新日 | 2024-03-06 | 実験手法 | X-RAY DIFFRACTION (2.55 Å) | 主引用文献 | Design, synthesis and optimization of 7-substituted-pyrazolo[4,3-b]pyridine ALK5 (activin receptor-like kinase 5) inhibitors. Bioorg. Med. Chem. Lett., 27, 2017
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7S1P
| PRMT5/MEP50 crystal structure with sinefungin bound | 分子名称: | Methylosome protein 50, Protein arginine N-methyltransferase 5, SINEFUNGIN | 著者 | Gunn, R.J, Thomas, N.C, Lawson, J.D, Ivetac, A, Kulyk, S, Smith, C.R, Marx, M.A. | 登録日 | 2021-09-02 | 公開日 | 2022-03-16 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.21 Å) | 主引用文献 | Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP -Deleted Cancers. J.Med.Chem., 65, 2022
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7SER
| PRMT5/MEP50 with compound 30 bound | 分子名称: | (2M)-2-{4-[4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl]-1-methyl-1H-pyrazol-5-yl}-1-benzothiophene-3-carbonitrile, 5'-DEOXY-5'-METHYLTHIOADENOSINE, Methylosome protein 50, ... | 著者 | Gunn, R.J, Thomas, N.C, Lawson, J.D, Ivetac, A, Smith, C.R, Kulyk, S, Marx, M.A. | 登録日 | 2021-10-01 | 公開日 | 2022-01-26 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.14 Å) | 主引用文献 | Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP -Deleted Cancers. J.Med.Chem., 65, 2022
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7SES
| PRMT5/MEP50 with compound 29 bound | 分子名称: | (2P)-2-{4-[4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl]-1-methyl-1H-pyrazol-5-yl}naphthalene-1-carbonitrile, 5'-DEOXY-5'-METHYLTHIOADENOSINE, Methylosome protein 50, ... | 著者 | Gunn, R.J, Thomas, N.C, Lawson, J.D, Ivetac, A, Smith, C.R, Kulyk, S, Marx, M.A. | 登録日 | 2021-10-01 | 公開日 | 2022-01-26 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.5 Å) | 主引用文献 | Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP -Deleted Cancers. J.Med.Chem., 65, 2022
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7RT1
| Crystal Structure of KRAS G12D with compound 15 (4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol) bound | 分子名称: | 4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol, GUANOSINE-5'-DIPHOSPHATE, Isoform 2B of GTPase KRas, ... | 著者 | Gunn, R.J, Thomas, N.C, Xiaolun, W, Lawson, J.D, Marx, M.A. | 登録日 | 2021-08-12 | 公開日 | 2021-12-22 | 最終更新日 | 2024-03-06 | 実験手法 | X-RAY DIFFRACTION (1.27 Å) | 主引用文献 | Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. J.Med.Chem., 65, 2022
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7RT5
| Crystal structure of KRAS G12D with compound 36 (4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-7-(8-ethynyl-7-fluoronaphthalen-1-yl)-8-fluoro-2-{[(4s,7as)-tetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidine) bound | 分子名称: | 4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-7-(8-ethynyl-7-fluoronaphthalen-1-yl)-8-fluoro-2-{[(4s,7as)-tetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidine, GUANOSINE-5'-DIPHOSPHATE, Isoform 2B of GTPase KRas, ... | 著者 | Gunn, R.J, Thomas, N.C, Xiaolun, W, Lawson, J.D, Marx, M.A. | 登録日 | 2021-08-12 | 公開日 | 2021-12-22 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (1.29 Å) | 主引用文献 | Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. J.Med.Chem., 65, 2022
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7RT2
| Crystal Structure of KRAS G12D with compound 25 (4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2R,4R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol) bound | 分子名称: | 1,2-ETHANEDIOL, 4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2R,4R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol, GLYCEROL, ... | 著者 | Gunn, R.J, Thomas, N.C, Xiaolun, W, Lawson, J.D, Marx, M.A. | 登録日 | 2021-08-12 | 公開日 | 2021-12-22 | 最終更新日 | 2024-03-06 | 実験手法 | X-RAY DIFFRACTION (1.59 Å) | 主引用文献 | Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. J.Med.Chem., 65, 2022
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7RT4
| KRAS G12D in complex with Compound 5B (7-(8-chloronaphthalen-1-yl)-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-4-(piperazin-1-yl)pyrido[4,3-d]pyrimidine) | 分子名称: | 7-(8-chloronaphthalen-1-yl)-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-4-(piperazin-1-yl)pyrido[4,3-d]pyrimidine, GLYCEROL, GUANOSINE-5'-DIPHOSPHATE, ... | 著者 | Gunn, R.J, Thomas, N.C, Xiaolun, W, Lawson, J.D, Marx, M.A. | 登録日 | 2021-08-12 | 公開日 | 2021-12-22 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.1 Å) | 主引用文献 | Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. J.Med.Chem., 65, 2022
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7RPZ
| KRAS G12D in complex with MRTX-1133 | 分子名称: | 4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2R,4R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)-5-ethynyl-6-fluoronaphthalen-2-ol, GUANOSINE-5'-DIPHOSPHATE, Isoform 2B of GTPase KRas, ... | 著者 | Gunn, R.J, Thomas, N.C, Xiaolun, W, Lawson, J.D, Marx, M.A. | 登録日 | 2021-08-05 | 公開日 | 2021-12-22 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (1.3 Å) | 主引用文献 | Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. J.Med.Chem., 65, 2022
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7RT3
| Crystal Structure of KRAS G12D with compound 24 (4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2S,4S,7aR)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol) bound | 分子名称: | 4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2S,4S,7aR)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol, GUANOSINE-5'-DIPHOSPHATE, Isoform 2B of GTPase KRas, ... | 著者 | Gunn, R.J, Thomas, N.C, Xiaolun, W, Lawson, J.D, Marx, M.A. | 登録日 | 2021-08-12 | 公開日 | 2021-12-22 | 最終更新日 | 2024-03-06 | 実験手法 | X-RAY DIFFRACTION (1.56 Å) | 主引用文献 | Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS G12D Inhibitor. J.Med.Chem., 65, 2022
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7S1R
| PRMT5/MEP50 crystal structure with MTA and a phthalazinone inhibitor bound (compound (M)-31) | 分子名称: | 5'-DEOXY-5'-METHYLTHIOADENOSINE, Methylosome protein 50, Protein arginine N-methyltransferase 5, ... | 著者 | Gunn, R.J, Thomas, N.C, Lawson, J.D, Ivetac, A, Kulyk, S, Smith, C.R, Marx, M.A. | 登録日 | 2021-09-02 | 公開日 | 2022-01-26 | 最終更新日 | 2023-10-18 | 実験手法 | X-RAY DIFFRACTION (2.1 Å) | 主引用文献 | Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP -Deleted Cancers. J.Med.Chem., 65, 2022
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