5IJ7
| Structure of Hs/AcPRC2 in complex with a pyridone inhibitor | Descriptor: | 5,8-dichloro-2-[(4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-({1-[(2R)-2-hydroxypropanoyl]piperidin-4-yl}oxy)-3,4-dihydroisoquinolin-1(2H)-one, Enhancer of Zeste Homolog 2 (EZH2),Histone-lysine N-methyltransferase EZH2, Polycomb protein EED, ... | Authors: | Gajiwala, K.S, Brooun, A, Deng, Y.-L, Liu, W. | Deposit date: | 2016-03-01 | Release date: | 2016-05-04 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (2.62 Å) | Cite: | Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance. Nat Commun, 7, 2016
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5IJ8
| Structure of the primary oncogenic mutant Y641N Hs/AcPRC2 in complex with a pyridone inhibitor | Descriptor: | 5,8-dichloro-2-[(4-ethyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-({1-[(2R)-2-hydroxypropanoyl]piperidin-4-yl}oxy)-3,4-dihydroisoquinolin-1(2H)-one, Enhancer of Zeste Homolog 2 (EZH2),Histone-lysine N-methyltransferase EZH2, Polycomb protein EED, ... | Authors: | Gajiwala, K.S, Brooun, A, Deng, Y.-L, Liu, W. | Deposit date: | 2016-03-01 | Release date: | 2016-05-04 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (2.99 Å) | Cite: | Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance. Nat Commun, 7, 2016
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4UXL
| Structure of Human ROS1 Kinase Domain in Complex with PF-06463922 | Descriptor: | (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile, PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ROS | Authors: | McTigue, M, Deng, Y, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2014-08-25 | Release date: | 2015-03-11 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (2.4 Å) | Cite: | Pf-06463922 is a Potent and Selective Next-Generation Ros1/Alk Inhibitor Capable of Blocking Crizotinib-Resistant Ros1 Mutations. Proc.Natl.Acad.Sci.USA, 112, 2015
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6CDT
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4W2R
| Structure of Hs/AcPRC2 in complex with 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one | Descriptor: | 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one, Enhancer of zeste 2 polycomb repressive complex 2 subunit, Polycomb protein EED, ... | Authors: | Gajiwala, K.S, Brooun, A, Liu, W, Deng, Y, Stewart, A.E. | Deposit date: | 2017-09-25 | Release date: | 2017-12-27 | Last modified: | 2023-09-27 | Method: | X-RAY DIFFRACTION (2.81 Å) | Cite: | Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J. Med. Chem., 61, 2018
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5AA8
| Structure of C1156Y,L1198F Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 ((10R)-7-amino-12-fluoro-2,10,16-trimethyl- 15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11) benzoxadiazacyclotetradecine-3-carbonitrile). | Descriptor: | (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile, ALK TYROSINE KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y.-L, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2015-07-23 | Release date: | 2016-06-08 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (1.86 Å) | Cite: | Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. N.Engl.J.Med., 374, 2016
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6B3W
| Structure of Hs/AcPRC2 in complex with 5,8-dichloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one | Descriptor: | 5,8-dichloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one, Enhancer of zeste 2 polycomb repressive complex 2 subunit,Enhancer of zeste 2 polycomb repressive complex 2 subunit, Polycomb protein EED, ... | Authors: | Gajiwala, K.S, Brooun, A, Liu, W, Deng, Y, Stewart, A.E. | Deposit date: | 2017-09-25 | Release date: | 2017-12-27 | Last modified: | 2023-10-04 | Method: | X-RAY DIFFRACTION (3.05 Å) | Cite: | Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J. Med. Chem., 61, 2018
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5AAC
| Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Complex with Crizotinib | Descriptor: | 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine, ALK TYROSINE KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2015-07-23 | Release date: | 2016-06-08 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (1.7 Å) | Cite: | Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. N.Engl.J.Med., 374, 2016
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5AA9
| Structure of L1198F Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 ((10R)-7-amino-12-fluoro-2,10,16-trimethyl- 15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11) benzoxadiazacyclotetradecine-3-carbonitrile). | Descriptor: | (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile, ALK TYROSINE KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y.-L, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2015-07-23 | Release date: | 2016-06-08 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (1.93 Å) | Cite: | Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. N.Engl.J.Med., 374, 2016
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5AAB
| Structure of C1156Y,L1198F Mutant Human Anaplastic Lymphoma Kinase in Complex with Crizotinib | Descriptor: | 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine, ALK TYROSINE KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2015-07-23 | Release date: | 2016-06-08 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (2.2 Å) | Cite: | Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. N.Engl.J.Med., 374, 2016
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5AAA
| Structure of L1198F Mutant Human Anaplastic Lymphoma Kinase in Complex with Crizotinib | Descriptor: | 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine, ALK TYROSINE KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2015-07-23 | Release date: | 2016-06-08 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (1.73 Å) | Cite: | Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. N.Engl.J.Med., 374, 2016
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5A9U
| Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 ((10R)-7-amino-12-fluoro-2,10,16-trimethyl- 15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11) benzoxadiazacyclotetradecine-3-carbonitrile). | Descriptor: | (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile, ALK TYROSINE KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y.-L, Liu, W, Brooun, A, Stewart, A. | Deposit date: | 2015-07-22 | Release date: | 2016-06-08 | Last modified: | 2024-01-10 | Method: | X-RAY DIFFRACTION (1.6 Å) | Cite: | Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. N.Engl.J.Med., 374, 2016
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4H6J
| Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction. | Descriptor: | ARYL HYDROCARBON NUCLEAR TRANSLOCATOR, HYPOXIA INDUCIBLE FACTOR 1-ALPHA | Authors: | Cardoso, R, Love, R.A, Nilsson, C, Bergqvist, S, Nowlin, D, Yan, J, Liu, K, Zhu, J, Chen, P, Deng, Y.-L, Dyson, H.J, Greig, M.J, Brooun, A. | Deposit date: | 2012-09-19 | Release date: | 2012-12-05 | Last modified: | 2024-02-28 | Method: | X-RAY DIFFRACTION (1.52 Å) | Cite: | Identification of Cys255 in HIF-1 alpha as a novel site for development of covalent inhibitors of HIF-1 alpha /ARNT PasB domain protein-protein interaction. Protein Sci., 21, 2012
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2FYG
| Crystal structure of NSP10 from Sars coronavirus | Descriptor: | GLYCEROL, Replicase polyprotein 1ab, ZINC ION | Authors: | Joseph, J.S, Saikatendu, K.S, Subramanian, V, Neuman, B.W, Brooun, A, Griffith, M, Moy, K, Yadav, M.K, Velasquez, J, Buchmeier, M.J, Stevens, R.C, Kuhn, P. | Deposit date: | 2006-02-07 | Release date: | 2006-08-08 | Last modified: | 2024-02-14 | Method: | X-RAY DIFFRACTION (1.8 Å) | Cite: | Crystal structure of nonstructural protein 10 from the severe acute respiratory syndrome coronavirus reveals a novel fold with two zinc-binding motifs. J.Virol., 80, 2006
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2QBX
| EphB2/SNEW Antagonistic Peptide Complex | Descriptor: | Ephrin type-B receptor 2, SULFATE ION, antagonistic peptide | Authors: | Chrencik, J.E, Brooun, A, Recht, M.I, Nicola, G, Pasquale, E.B, Kuhn, P, Accelerated Technologies Center for Gene to 3D Structure (ATCG3D) | Deposit date: | 2007-06-18 | Release date: | 2007-11-06 | Last modified: | 2023-08-30 | Method: | X-RAY DIFFRACTION (2.3 Å) | Cite: | Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition. J.Biol.Chem., 282, 2007
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2HLE
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5KZ0
| Structure of Human Anaplastic Lymphoma Kinase in Complex With 2-[(1R)-1-{[2-amino-5-(1,3-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl]oxy}ethyl]-4-fluoro-N,N-dimethylbenzamide | Descriptor: | 2-[(1~{R})-1-[2-azanyl-5-(1,3-dimethylpyrazol-4-yl)pyridin-3-yl]oxyethyl]-4-fluoranyl-~{N},~{N}-dimethyl-benzamide, ALK tyrosine kinase receptor | Authors: | McTigue, M, Deng, Y.L, Liu, W, Brooun, A. | Deposit date: | 2016-07-22 | Release date: | 2016-08-17 | Last modified: | 2023-10-04 | Method: | X-RAY DIFFRACTION (2.3 Å) | Cite: | Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J. Med. Chem., 57, 2014
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2YFX
| Structure of L1196M Mutant Anaplastic Lymphoma Kinase in Complex with Crizotinib | Descriptor: | 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine, TYROSINE-PROTEIN KINASE RECEPTOR | Authors: | McTigue, M, Deng, Y, Liu, W, Brooun, A. | Deposit date: | 2011-04-08 | Release date: | 2011-05-04 | Last modified: | 2023-12-20 | Method: | X-RAY DIFFRACTION (1.7 Å) | Cite: | Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib. J.Med.Chem., 57, 2014
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7K6O
| Crystal structure of PI3Kalpha inhibitor 10-5429 | Descriptor: | (3S)-3-[4-(2-aminopyrimidin-5-yl)-2-(morpholin-4-yl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-N-methylpyrrolidine-1-sulfonamide, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | Authors: | Chen, P, Brooun, A, Deng, Y.L, Grodsky, N, Kaiser, S.E. | Deposit date: | 2020-09-21 | Release date: | 2021-01-06 | Last modified: | 2024-04-03 | Method: | X-RAY DIFFRACTION (2.738 Å) | Cite: | Structure-Based Drug Design and Synthesis of PI3K alpha-Selective Inhibitor (PF-06843195). J.Med.Chem., 64, 2021
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7K71
| Crystal structure of PI3Kalpha inhibitor 4-0686 | Descriptor: | 2-(morpholin-4-yl)[4,5'-bipyrimidin]-2'-amine, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | Authors: | Chen, P, Brooun, A, Deng, Y.L, Grodsky, N, Kaiser, S.E. | Deposit date: | 2020-09-21 | Release date: | 2021-01-06 | Last modified: | 2024-04-03 | Method: | X-RAY DIFFRACTION (2.9 Å) | Cite: | Structure-Based Drug Design and Synthesis of PI3K alpha-Selective Inhibitor (PF-06843195). J.Med.Chem., 64, 2021
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7K6N
| Crystal structure of PI3Kalpha selective Inhibitor 11-1575 | Descriptor: | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, tert-butyl (3S)-3-[4-(2-aminopyrimidin-5-yl)-2-(morpholin-4-yl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate | Authors: | Chen, P, Brooun, A, Deng, Y.L, Grodsky, N, Kaiser, S.E. | Deposit date: | 2020-09-21 | Release date: | 2021-01-06 | Last modified: | 2024-04-03 | Method: | X-RAY DIFFRACTION (2.77 Å) | Cite: | Structure-Based Drug Design and Synthesis of PI3K alpha-Selective Inhibitor (PF-06843195). J.Med.Chem., 64, 2021
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7K6M
| Crystal structure of PI3Kalpha selective Inhibitor PF-06843195 | Descriptor: | 2,2-difluoroethyl (3S)-3-{[2'-amino-5-fluoro-2-(morpholin-4-yl)[4,5'-bipyrimidin]-6-yl]amino}-3-(hydroxymethyl)pyrrolidine-1-carboxylate, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | Authors: | Chen, P, Brooun, A, Deng, Y.L, Grodsky, N, Kaiser, S.E. | Deposit date: | 2020-09-21 | Release date: | 2021-01-06 | Last modified: | 2024-04-03 | Method: | X-RAY DIFFRACTION (2.413 Å) | Cite: | Structure-Based Drug Design and Synthesis of PI3K alpha-Selective Inhibitor (PF-06843195). J.Med.Chem., 64, 2021
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3BJI
| Structural Basis of Promiscuous Guanine Nucleotide Exchange by the T-Cell Essential Vav1 | Descriptor: | Proto-oncogene vav, Ras-related C3 botulinum toxin substrate 1 precursor, ZINC ION | Authors: | Chrencik, J.E, Brooun, A, Kuhn, P, Accelerated Technologies Center for Gene to 3D Structure (ATCG3D) | Deposit date: | 2007-12-04 | Release date: | 2008-07-15 | Last modified: | 2024-03-13 | Method: | X-RAY DIFFRACTION (2.6 Å) | Cite: | Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1. J.Mol.Biol., 380, 2008
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2YHV
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2YJR
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