3PIX
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7N5Y
| Fragment-Based Drug Design of a Novel, Covalent Bruton's Tyrosine Kinase Inhibitor | Descriptor: | 5-(1-{[(3S)-1-propanoylpyrrolidin-3-yl]oxy}isoquinolin-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one, DIMETHYL SULFOXIDE, IMIDAZOLE, ... | Authors: | Dougan, D.R, Lawson, J.D. | Deposit date: | 2021-06-07 | Release date: | 2021-09-08 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (1.85 Å) | Cite: | 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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5FBO
| BTK-inhibitor co-structure | Descriptor: | 4-[8-azanyl-3-[(2~{S})-1-[4-(dimethylamino)butanoyl]pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-~{N}-(1,3-thiazol-2-yl)benzamide, 4-[8-azanyl-3-[(3~{R},6~{S})-1-cyclopropylcarbonyl-6-methyl-piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoranyl-~{N}-[4-(trifluoromethyl)pyridin-2-yl]benzamide, Tyrosine-protein kinase BTK | Authors: | Fischmann, T.O. | Deposit date: | 2015-12-14 | Release date: | 2016-03-23 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (1.894 Å) | Cite: | Discovery of 8-Amino-imidazo[1,5-a]pyrazines as Reversible BTK Inhibitors for the Treatment of Rheumatoid Arthritis. ACS Med Chem Lett, 7, 2016
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8U2E
| Bruton's tyrosine kinase in complex with N-[(2R)-1-[(3R)-3-(methylcarbamoyl)-1H,2H,3H,4H,9H-pyrido[3,4-b]indol-2-yl]-3-(3-methylphenyl)-1-oxopropan-2-yl]-1H-indazole-5-carboxamide | Descriptor: | (2S)-6-fluoro-5-[(3S)-3-(3-methyl-2-oxoimidazolidin-1-yl)piperidin-1-yl]-2-(4-methylpiperazine-1-carbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide, 1,2-ETHANEDIOL, CHLORIDE ION, ... | Authors: | Gajewski, S, Clifton, M.C. | Deposit date: | 2023-09-05 | Release date: | 2024-01-31 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (1.9 Å) | Cite: | Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton's Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies. J.Med.Chem., 67, 2024
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6X3O
| Co-structure of BTK kinase domain with L-005191930 inhibitor | Descriptor: | 4-[8-azanyl-3-[(2~{S})-1-[4-(dimethylamino)butanoyl]pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-~{N}-(1,3-thiazol-2-yl)benzamide, 4-{8-amino-3-[(6R,8aS)-3-oxo-3,5,6,7,8,8a-hexahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}-3-methoxy-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide, Tyrosine-protein kinase BTK | Authors: | Fischmann, T.O. | Deposit date: | 2020-05-21 | Release date: | 2020-07-22 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (1.9 Å) | Cite: | Potent, non-covalent reversible BTK inhibitors with 8-amino-imidazo[1,5-a]pyrazine core featuring 3-position bicyclic ring substitutes. Bioorg.Med.Chem.Lett., 30, 2020
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8GC7
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6BIK
| BTK complex with compound 7 | Descriptor: | 4-tert-butyl-N-[2-(hydroxymethyl)-3-(1-methyl-5-{[5-(morpholine-4-carbonyl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridazin-3-yl)phenyl]benzamide, GLYCEROL, SULFATE ION, ... | Authors: | Kiefer, J.R, Eigenbrot, C, Yu, C.L. | Deposit date: | 2017-11-02 | Release date: | 2018-11-07 | Last modified: | 2019-03-27 | Method: | X-RAY DIFFRACTION (1.901 Å) | Cite: | Water molecules in protein-ligand interfaces. Evaluation of software tools and SAR comparison. J. Comput. Aided Mol. Des., 33, 2019
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8E2M
| Bruton's tyrosine kinase (BTK) with compound 13 | Descriptor: | (5P)-5-[4-methyl-6-(2-methylpropyl)pyridin-3-yl]-4-oxo-N-[(1R,2S)-2-propanamidocyclopentyl]-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide, TRIETHYLENE GLYCOL, Tyrosine-protein kinase BTK | Authors: | Alexander, R, Milligan, C.M. | Deposit date: | 2022-08-15 | Release date: | 2022-11-16 | Last modified: | 2024-04-03 | Method: | X-RAY DIFFRACTION (1.904 Å) | Cite: | Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J.Med.Chem., 65, 2022
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6YYF
| Crystal Structure of 5-chloroindoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C | Descriptor: | 5-chloranyl-1,3-dihydroindol-2-one, MAGNESIUM ION, Tyrosine-protein kinase BTK, ... | Authors: | Brear, P, Wagstaff, J, Hyvonen, M. | Deposit date: | 2020-05-05 | Release date: | 2021-05-12 | Last modified: | 2024-01-24 | Method: | X-RAY DIFFRACTION (1.93 Å) | Cite: | Optimising crystallographic systems for structure-guided drug discovery To Be Published
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7R60
| BTK in complex with 18A | Descriptor: | 2-(4-phenoxyphenoxy)-5-[(3R)-1-(prop-2-enoyl)piperidin-3-yl]pyridine-3-carboxamide, Tyrosine-protein kinase BTK | Authors: | Gardberg, A. | Deposit date: | 2021-06-22 | Release date: | 2021-10-06 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (1.94 Å) | Cite: | Discovery of Covalent Bruton's Tyrosine Kinase Inhibitors with Decreased CYP2C8 Inhibitory Activity. Chemmedchem, 16, 2021
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3K54
| Structures of human Bruton's tyrosine kinase in active and inactive conformations suggests a mechanism of activation for TEC family kinases. | Descriptor: | N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE, Tyrosine-protein kinase BTK | Authors: | Marcotte, D.J, Liu, Y.-T, Arduini, R.M, Hession, C.A, Miatkowski, K, Wildes, C.P, Cullen, P.F, Hopkins, B.T, Mertsching, E, Jenkins, T.J, Romanowski, M.J, Baker, D.P, Silvian, L.F. | Deposit date: | 2009-10-06 | Release date: | 2010-01-19 | Last modified: | 2023-09-06 | Method: | X-RAY DIFFRACTION (1.94 Å) | Cite: | Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases. Protein Sci., 19, 2010
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7KXO
| BTK1 SOAKED WITH COMPOUND 24 | Descriptor: | 3-tert-butyl-N-[(1R)-6-{2-[5-methyl-1-(oxan-4-yl)-1H-pyrazol-4-yl]-3H-imidazo[4,5-b]pyridin-7-yl}-1,2,3,4-tetrahydronaphthalen-1-yl]-1,2,4-oxadiazole-5-carboxamide, DIMETHYL SULFOXIDE, Isoform BTK-C of Tyrosine-protein kinase BTK | Authors: | Viacava Follis, A. | Deposit date: | 2020-12-04 | Release date: | 2021-05-19 | Last modified: | 2023-10-18 | Method: | X-RAY DIFFRACTION (1.94 Å) | Cite: | Discovery of potent and selective reversible Bruton's tyrosine kinase inhibitors. Bioorg.Med.Chem., 40, 2021
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8U2D
| Bruton's tyrosine kinase in complex with N-[(2R)-1-[(3R)-3-(methylcarbamoyl)-1H,2H,3H,4H,9H-pyrido[3,4-b]indol-2-yl]-3-(3-methylphenyl)-1-oxopropan-2-yl]-1H-indazole-5-carboxamide | Descriptor: | (3R)-2-[N-(1H-indazole-5-carbonyl)-3-methyl-D-phenylalanyl]-N-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxamide, 1,2-ETHANEDIOL, CHLORIDE ION, ... | Authors: | Gajewski, S, Clifton, M.C. | Deposit date: | 2023-09-05 | Release date: | 2024-01-31 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton's Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies. J.Med.Chem., 67, 2024
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4OTF
| Crystal structure of the kinase domain of Bruton's Tyrosine kinase with GDC0834 | Descriptor: | N-{3-[6-({4-[(2R)-1,4-dimethyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl }-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide, SULFATE ION, Tyrosine-protein kinase BTK | Authors: | Hymowitz, S.G, Maurer, B. | Deposit date: | 2014-02-13 | Release date: | 2015-01-28 | Last modified: | 2023-12-06 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Potent and selective Bruton's tyrosine kinase inhibitors: Discovery of GDC-0834. Bioorg.Med.Chem.Lett., 25, 2015
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5P9H
| BTK1 COCRYSTALLIZED WITH RN983 | Descriptor: | 6-~{tert}-butyl-8-fluoranyl-2-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-(1-methylpiperidin-4-yl)pyridin-2-yl]amino]-6-oxidanylidene-pyridazin-3-yl]pyridin-2-yl]phthalazin-1-one, Tyrosine-protein kinase BTK | Authors: | Gardberg, A.S. | Deposit date: | 2016-09-20 | Release date: | 2017-05-24 | Last modified: | 2024-05-22 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Ability of Bruton's Tyrosine Kinase Inhibitors to Sequester Y551 and Prevent Phosphorylation Determines Potency for Inhibition of Fc Receptor but not B-Cell Receptor Signaling. Mol. Pharmacol., 91, 2017
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6X3N
| Co-structure of BTK kinase domain with L-005085737 inhibitor | Descriptor: | 4-[8-azanyl-3-[(2~{S})-1-[4-(dimethylamino)butanoyl]pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-~{N}-(1,3-thiazol-2-yl)benzamide, 4-{8-amino-3-[(6R,8aS)-3-oxohexahydro-3H-[1,3]oxazolo[3,4-a]pyridin-6-yl]imidazo[1,5-a]pyrazin-1-yl}-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide, Tyrosine-protein kinase BTK | Authors: | Fischmann, T.O. | Deposit date: | 2020-05-21 | Release date: | 2020-07-22 | Last modified: | 2024-03-06 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Potent, non-covalent reversible BTK inhibitors with 8-amino-imidazo[1,5-a]pyrazine core featuring 3-position bicyclic ring substitutes. Bioorg.Med.Chem.Lett., 30, 2020
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4OTR
| Crystal structure of BTK kinase domain complexed with 6-cyclopropyl-2-[3-[5-[[5-(4-ethylpiperazin-1-yl)-2-pyridyl]amino]-1-methyl-6-oxo-3-pyridyl]-2-(hydroxymethyl)phenyl]-8-fluoro-isoquinolin-1-one | Descriptor: | 6-cyclopropyl-2-[3-(5-{[5-(4-ethylpiperazin-1-yl)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(hydroxymethyl)phenyl]-8-fluoroisoquinolin-1(2H)-one, DIMETHYL SULFOXIDE, Tyrosine-protein kinase BTK | Authors: | Kuglstatter, A, Wong, A. | Deposit date: | 2014-02-14 | Release date: | 2014-05-14 | Last modified: | 2023-09-20 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Structure-Based Drug Design of RN486, a Potent and Selective Bruton's Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis. J.Med.Chem., 58, 2015
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3OCT
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6BKE
| BTK complex with compound 10 | Descriptor: | N-[2-(2-hydroxyethyl)-3-{5-[(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-1,6-dihydropyridazin-3-yl}phenyl]-1-benzothiophene-2-carboxamide, SULFATE ION, Tyrosine-protein kinase BTK | Authors: | Kiefer, J.R, Eigenbrot, C, Yu, C.L, Wang, G.X. | Deposit date: | 2017-11-08 | Release date: | 2018-11-07 | Last modified: | 2019-03-27 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Water molecules in protein-ligand interfaces. Evaluation of software tools and SAR comparison. J. Comput. Aided Mol. Des., 33, 2019
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6YYG
| Crystal Structure of 5-(trifluoromethoxy)indoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C | Descriptor: | 5-(trifluoromethyloxy)-1,3-dihydroindol-2-one, MAGNESIUM ION, Tyrosine-protein kinase BTK, ... | Authors: | Brear, P, Wagstaff, J, Hyvonen, M. | Deposit date: | 2020-05-05 | Release date: | 2021-05-12 | Last modified: | 2024-01-24 | Method: | X-RAY DIFFRACTION (1.95 Å) | Cite: | Optimising crystallographic systems for structure-guided drug discovery To Be Published
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5JRS
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6DI3
| CRYSTAL STRUCTURE OF BTK IN COMPLEX WITH FRAGMENT LIGAND | Descriptor: | 6-[(3S)-3-(acryloylamino)pyrrolidin-1-yl]-2-(4-phenoxyphenoxy)pyridine-3-carboxamide, Tyrosine-protein kinase BTK | Authors: | GARDBERG, A. | Deposit date: | 2018-05-22 | Release date: | 2018-09-05 | Last modified: | 2024-03-13 | Method: | X-RAY DIFFRACTION (2 Å) | Cite: | Discovery of potent, highly selective covalent irreversible BTK inhibitors from a fragment hit. Bioorg. Med. Chem. Lett., 28, 2018
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3PJ1
| Crystal structure of BTK kinase domain complexed with 3-(2,6-Dichloro-phenyl)-7-[4-(2-diethylamino-ethoxy)-phenylamino]-1-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one | Descriptor: | 3-(2,6-dichlorophenyl)-7-({4-[2-(diethylamino)ethoxy]phenyl}amino)-1-methyl-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, Tyrosine-protein kinase BTK | Authors: | Kuglstatter, A, Wong, A. | Deposit date: | 2010-11-08 | Release date: | 2011-01-12 | Last modified: | 2023-09-06 | Method: | X-RAY DIFFRACTION (2 Å) | Cite: | Insights into the conformational flexibility of Bruton's tyrosine kinase from multiple ligand complex structures. Protein Sci., 20, 2011
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6TFP
| BTK in complex with LOU064, a potent and highly selective covalent inhibitor | Descriptor: | SODIUM ION, Tyrosine-protein kinase BTK, ~{N}-[3-[6-azanyl-5-[2-[methyl(propanoyl)amino]ethoxy]pyrimidin-4-yl]-5-fluoranyl-2-methyl-phenyl]-4-cyclopropyl-2-fluoranyl-benzamide | Authors: | Scheufler, C, Hinniger, A, Gutmann, S. | Deposit date: | 2019-11-14 | Release date: | 2020-03-04 | Last modified: | 2024-05-01 | Method: | X-RAY DIFFRACTION (2 Å) | Cite: | Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J.Med.Chem., 63, 2020
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4ZLZ
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