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5UUU
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DESIGN, SYNTHESIS, AND EVALUATION OF THE FIRST SELECTIVE AND POTENT G-PROTEIN-COUPLED RECEPTOR KINASE 2 (GRK2) INHIBITOR FOR THE POTENTIAL TREATMENT OF HEART FAILURE
Descriptor:Beta-adrenergic receptor kinase 1, 3-({[4-methyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]methyl}amino)-N-[2-(trifluoromethyl)benzyl]benzamide, SULFATE ION, ...
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2017-02-17
Release date:2017-07-26
Last modified:2017-09-06
Method:X-RAY DIFFRACTION (2.7 Å)
Cite:Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure.
J. Med. Chem., 60, 2017
5UVC
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DESIGN, SYNTHESIS, AND EVALUATION OF THE FIRST SELECTIVE AND POTENT G-PROTEIN-COUPLED RECEPTOR KINASE 2 (GRK2) INHIBITOR FOR THE POTENTIAL TREATMENT OF HEART FAILURE
Descriptor:Beta-adrenergic receptor kinase 1, N-benzyl-3-({[5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]methyl}amino)benzamide, SULFATE ION
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2017-02-20
Release date:2017-07-26
Last modified:2017-09-06
Method:X-RAY DIFFRACTION (2.65 Å)
Cite:Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure.
J. Med. Chem., 60, 2017
5VP0
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DISCOVERY OF CLINICAL CANDIDATE N-{(1S)-1-[3-FLUORO-4-(TRIFLUOROMETHOXY)PHENYL]-2-METHOXYETHYL}-7-METHOXY-2-OXO-2,3-DIHYDROPYRIDO[2,3-B]PYRAZINE-4(1H)-CARBOXAMIDE (TAK-915), A HIGHLY POTENT, SELECTIVE, AND BRAIN-PENETRATING PHOSPHODIESTERASE 2A INHIBITOR FOR THE TREATMENT OF COGNITIVE DISORDERS
Descriptor:cGMP-dependent 3',5'-cyclic phosphodiesterase, ZINC ION, MAGNESIUM ION, ...
Authors:Hoffman, I.D.
Deposit date:2017-05-03
Release date:2017-08-23
Last modified:2017-10-11
Method:X-RAY DIFFRACTION (2.2 Å)
Cite:Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders.
J. Med. Chem., 60, 2017
5VP1
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DISCOVERY OF CLINICAL CANDIDATE N-{(1S)-1-[3-FLUORO-4-(TRIFLUOROMETHOXY)PHENYL]-2-METHOXYETHYL}-7-METHOXY-2-OXO-2,3-DIHYDROPYRIDO[2,3-B]PYRAZINE-4(1H)-CARBOXAMIDE (TAK-915), A HIGHLY POTENT, SELECTIVE, AND BRAIN-PENETRATING PHOSPHODIESTERASE 2A INHIBITOR FOR THE TREATMENT OF COGNITIVE DISORDERS
Descriptor:cGMP-dependent 3',5'-cyclic phosphodiesterase, ZINC ION, MAGNESIUM ION, ...
Authors:Hoffman, I.D.
Deposit date:2017-05-03
Release date:2017-12-27
Last modified:2018-05-23
Method:X-RAY DIFFRACTION (1.86 Å)
Cite:Discovery of a Novel Series of Pyrazolo[1,5-a]pyrimidine-Based Phosphodiesterase 2A Inhibitors Structurally Different from N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), for the Treatment of Cognitive Disorders.
Chem. Pharm. Bull., 65, 2017
2NP8
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STRUCTURAL BASIS FOR THE INHIBITION OF AURORA A KINASE BY A NOVEL CLASS OF HIGH AFFINITY DISUBSTITUTED PYRIMIDINE INHIBITORS
Descriptor:Serine/threonine-protein kinase 6, SULFATE ION, N-{3-[(4-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}PYRIMIDIN-2-YL)AMINO]PHENYL}CYCLOPROPANECARBOXAMIDE
Authors:Tari, L.W., Hoffman, I.D., Bensen, D.C., Hunter, M.J., Nix, J., Nelson, K.J., McRee, D.E., Swanson, R.V.
Deposit date:2006-10-26
Release date:2006-12-26
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.25 Å)
Cite:Structural basis for the inhibition of Aurora A kinase by a novel class of high affinity disubstituted pyrimidine inhibitors.
Bioorg.Med.Chem.Lett., 17, 2007
5TR6
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DISCOVERY OF TAK-659, AN ORALLY AVAILABLE INVESTIGATIONAL INHIBITOR OF SPLEEN TYROSINE KINASE (SYK)
Descriptor:Tyrosine-protein kinase SYK, 6-{[(1R,2S)-2-aminocyclohexyl]amino}-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one, 1,2-ETHANEDIOL
Authors:Yano, J., Jennings, A., Lam, B., Hoffman, I.D.
Deposit date:2016-10-25
Release date:2016-11-30
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (1.93 Å)
Cite:Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK).
Bioorg. Med. Chem. Lett., 26, 2016
5TT7
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DISCOVERY OF TAK-659, AN ORALLY AVAILABLE INVESTIGATIONAL INHIBITOR OF SPLEEN TYROSINE KINASE (SYK)
Descriptor:Tyrosine-protein kinase SYK, 2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(3-methylphenyl)amino]-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one
Authors:Yano, J., Jennings, A., Lam, B., Hoffman, I.D.
Deposit date:2016-11-01
Release date:2016-11-30
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (1.77 Å)
Cite:Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK).
Bioorg. Med. Chem. Lett., 26, 2016
5TC0
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STRUCTURE-BASED OPTIMIZATION OF 1H-IMIDAZOLE-2-CARBOXAMIDES AS AXL KINASE INHIBITORS UTILIZING A MER MUTANT SURROGATE
Descriptor:Tyrosine-protein kinase Mer, N-(2-{4-[(2S)-4-(methylsulfonyl)morpholin-2-yl]-1,3-thiazol-2-yl}phenyl)-1H-imidazole-2-carboxamide
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2016-09-13
Release date:2017-01-25
Method:X-RAY DIFFRACTION (2.24 Å)
Cite:Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate.
Bioorg. Med. Chem. Lett., 27, 2017
5TD2
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STRUCTURE-BASED OPTIMIZATION OF 1H-IMIDAZOLE-2-CARBOXAMIDES AS AXL KINASE INHIBITORS UTILIZING A MER MUTANT SURROGATE
Descriptor:Tyrosine-protein kinase Mer, N-[2-{4-[(2S)-4-(methylsulfonyl)morpholin-2-yl]-1,3-thiazol-2-yl}-4-(morpholin-4-yl)phenyl]-1H-imidazole-2-carboxamide
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2016-09-16
Release date:2017-01-25
Method:X-RAY DIFFRACTION (2.68 Å)
Cite:Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate.
Bioorg. Med. Chem. Lett., 27, 2017
5U7Q
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IDENTIFICATION OF A NEW CLASS OF POTENT CDC7 INHIBITORS DESIGNED BY PUTATIVE PHARMACOPHORE MODEL: SYNTHESIS AND BIOLOGICAL EVALUATION OF 2,3-DIHYDROTHIENO[3,2-D]PYRIMIDIN-4(1H)-ONES
Descriptor:Rho-associated protein kinase 2
Authors:Hoffman, I.D.
Deposit date:2016-12-12
Release date:2017-03-29
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (3.15 Å)
Cite:Identification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones.
Bioorg. Med. Chem., 25, 2017
5U7R
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IDENTIFICATION OF A NEW CLASS OF POTENT CDC7 INHIBITORS DESIGNED BY PUTATIVE PHARMACOPHORE MODEL: SYNTHESIS AND BIOLOGICAL EVALUATION OF 2,3-DIHYDROTHIENO[3,2-D]PYRIMIDIN-4(1H)-ONES
Descriptor:Rho-associated protein kinase 2, (1s,4s)-4-(4-fluorophenyl)-4-hydroxy-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one
Authors:Hoffman, I.D., Skene, R.J.
Deposit date:2016-12-12
Release date:2017-03-29
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (3.33 Å)
Cite:Identification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones.
Bioorg. Med. Chem., 25, 2017
5UAB
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MET TYROSINE KINASE INHIBITION ENHANCES THE ANTITUMOR EFFICACY OF AN HGF ANTIBODY
Descriptor:Hepatocyte growth factor receptor, N-{6-[([1,2,4]triazolo[4,3-a]pyridin-3-yl)sulfanyl]imidazo[1,2-b]pyridazin-2-yl}cyclopropanecarboxamide, GLYCEROL, ...
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2016-12-19
Release date:2017-05-31
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (1.9 Å)
Cite:MET Tyrosine Kinase Inhibition Enhances the Antitumor Efficacy of an HGF Antibody.
Mol. Cancer Ther., 16, 2017
5UAD
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MET TYROSINE KINASE INHIBITION ENHANCES THE ANTITUMOR EFFICACY OF AN HGF ANTIBODY
Descriptor:Hepatocyte growth factor receptor, N-(6-{[6-(1-methyl-1H-pyrazol-4-yl)-1H-benzotriazol-1-yl]methyl}imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide, CHLORIDE ION
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2016-12-19
Release date:2017-05-31
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (2.25 Å)
Cite:MET Tyrosine Kinase Inhibition Enhances the Antitumor Efficacy of an HGF Antibody.
Mol. Cancer Ther., 16, 2017
5UAF
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MET TYROSINE KINASE INHIBITION ENHANCES THE ANTITUMOR EFFICACY OF AN HGF ANTIBODY
Descriptor:Hepatocyte growth factor receptor, N-(6-{[6-(1-methyl-1H-pyrazol-4-yl)-1H-benzotriazol-1-yl]methyl}imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide, CHLORIDE ION
Authors:Hoffman, I.D., Lawson, J.D.
Deposit date:2016-12-19
Release date:2017-05-31
Last modified:2017-11-22
Method:X-RAY DIFFRACTION (2.25 Å)
Cite:MET Tyrosine Kinase Inhibition Enhances the Antitumor Efficacy of an HGF Antibody.
Mol. Cancer Ther., 16, 2017
6BR2
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STRUCTURE OF RORGT IN COMPLEX WITH A NOVEL ISOQUINOLINE INVERSE AGONIST.
Descriptor:Nuclear receptor ROR-gamma, (4S)-2-METHYL-2,4-PENTANEDIOL, (1R)-N-(4-tert-butyl-3-fluorophenyl)-6-methoxy-2-[(3-oxo-2,3-dihydro-1,2-oxazol-5-yl)acetyl]-1,2,3,4-tetrahydroisoquinoline-1-carboxamide
Authors:Skene, R.J., Hoffman, I.
Deposit date:2017-11-29
Release date:2018-03-21
Last modified:2018-04-25
Method:X-RAY DIFFRACTION (3.18 Å)
Cite:Discovery of [ cis-3-({(5 R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1 H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5 H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor gamma t Inverse Agonist.
J. Med. Chem., 61, 2018
6BR3
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STRUCTURE OF RORGT IN COMPLEX WITH A NOVEL INVERSE AGONIST TAK-828.
Descriptor:Nuclear receptor ROR-gamma, (4S)-2-METHYL-2,4-PENTANEDIOL, {cis-3-[(5R)-5-[(7-fluoro-1,1-dimethyl-1H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carbonyl]cyclobutyl}acetic acid
Authors:Skene, R.J., Hoffman, I.
Deposit date:2017-11-29
Release date:2018-03-21
Last modified:2018-04-25
Method:X-RAY DIFFRACTION (3 Å)
Cite:Discovery of [ cis-3-({(5 R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1 H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5 H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor gamma t Inverse Agonist.
J. Med. Chem., 61, 2018
3HF6
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CRYSTAL STRUCTURE OF HUMAN TRYPTOPHAN HYDROXYLASE TYPE 1 WITH BOUND LP-521834 AND FE
Descriptor:Tryptophan 5-hydroxylase 1, FE (III) ION, 4-(4-amino-6-{[(1R)-1-naphthalen-2-ylethyl]amino}-1,3,5-triazin-2-yl)-L-phenylalanine
Authors:Tari, L.W., Swanson, R.V., Hunter, M.J.
Deposit date:2009-05-11
Release date:2009-11-24
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (1.8 Å)
Cite:Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-crystal Structures and Kinetic Analysis
Curr Chem Genomics, 4, 2010
3HF8
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CRYSTAL STRUCTURE OF HUMAN TRYOPTOPHAN HYDROXYLASE TYPE 1 WITH BOUND LP-533401 AND FE
Descriptor:Tryptophan 5-hydroxylase 1, FE (III) ION, 4-{2-amino-6-[(1R)-2,2,2-trifluoro-1-(3'-fluorobiphenyl-4-yl)ethoxy]pyrimidin-4-yl}-L-phenylalanine
Authors:Tari, L.W., Swanson, R.V., Hunter, M.J.
Deposit date:2009-05-11
Release date:2010-04-21
Last modified:2012-03-28
Method:X-RAY DIFFRACTION (1.85 Å)
Cite:Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-crystal Structures and Kinetic Analysis.
Curr Chem Genomics, 4, 2010
3HFB
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CRYSTAL STRUCTURE OF HUMAN TRYOPTOPHAN HYDROXYLASE TYPE 1 WITH LP-534193
Descriptor:Tryptophan 5-hydroxylase 1, FE (III) ION, 4-(5-{[(2'-methylbiphenyl-2-yl)methyl]amino}pyrazin-2-yl)-L-phenylalanine
Authors:Tari, L.W., Swanson, R.V., Hunter, M.J.
Deposit date:2009-05-11
Release date:2010-04-21
Last modified:2012-03-28
Method:X-RAY DIFFRACTION (1.92 Å)
Cite:Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-crystal Structures and Kinetic Analysis.
Curr Chem Genomics, 4, 2010