Author results

2UWD
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INHIBITION OF THE HSP90 MOLECULAR CHAPERONE IN VITRO AND IN VIVO BY NOVEL, SYNTHETIC, POTENT RESORCINYLIC PYRAZOLE, ISOXAZOLE AMIDE ANALOGS
Descriptor:HEAT SHOCK PROTEIN HSP 90-ALPHA, MAGNESIUM ION, SULFATE ION, ...
Authors:Sharp, S.Y., Prodromou, C., Boxall, K., Powers, M.V., Holmes, J.L., Box, G., Matthews, T.P., Cheung, K.M., Kalusa, A., James, K., Hayes, A., Hardcastle, A., Dymock, B., Brough, P.A., Barril, X., Cansfield, J.E., Wright, L.M., Surgenor, A., Foloppe, N., Aherne, W., Pearl, L., Jones, K., McDonald, E., Raynaud, F., Eccles, S., Drysdale, M., Workman, P.
Deposit date:2007-03-20
Release date:2007-04-24
Last modified:2018-02-28
Method:X-RAY DIFFRACTION (1.9 Å)
Cite:Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues.
Mol. Cancer Ther., 6, 2007
2VCI
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4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER
Descriptor:HEAT SHOCK PROTEIN HSP 90-ALPHA, 5-[2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL]-N-ETHYL-4-[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ISOXAZOLE-3-CARBOXAMIDE
Authors:Brough, P.A., Aherne, W., Barril, X., Borgognoni, J., Boxal, K., Cansfield, J.E., Cheung, K.M., Collins, I., Davies, N.G.M., Drysdale, M.J., Dymock, B., Eccles, S.A., Finch, H., Fink, A., Hayes, A., Howes, R., Hubbard, R.E., James, K., Jordan, A.M., Lockie, A., Martins, V., Massey, A., Matthews, T.P., McDonald, E., Northfield, C.J., Pearl, L.H., Prodromou, C., Ray, S., Raynaud, F.I., Roughley, S.D., Sharp, S.Y., Surgenor, A., Walmsley, D.L., Webb, P., Wood, M., Workman, P., Wright, L.
Deposit date:2007-09-24
Release date:2007-12-11
Last modified:2018-02-28
Method:X-RAY DIFFRACTION (2 Å)
Cite:4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer.
J. Med. Chem., 51, 2008
2VCJ
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4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER
Descriptor:HEAT SHOCK PROTEIN HSP 90-ALPHA, 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]isoxazole-3-carboxamide
Authors:Brough, P.A., Aherne, W., Barril, X., Borgognoni, J., Boxal, K., Cansfield, J.E., Cheung, K.M., Collins, I., Davies, N.G.M., Drysdale, M.J., Dymock, B., Eccles, S.A., Finch, H., Fink, A., Hayes, A., Howes, R., Hubbard, R.E., James, K., Jordan, A.M., Lockie, A., Martins, V., Massey, A., Matthews, T.P., McDonald, E., Northfield, C.J., Pearl, L.H., Prodromou, C., Ray, S., Raynaud, F.I., Roughley, S.D., Sharp, S.Y., Surgenor, A., Walmsley, D.L., Webb, P., Wood, M., Workman, P., Wright, L.
Deposit date:2007-09-24
Release date:2007-12-11
Last modified:2018-02-28
Method:X-RAY DIFFRACTION (2.5 Å)
Cite:4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer.
J. Med. Chem., 51, 2008
2X39
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STRUCTURE OF 4-AMINO-N-(4-CHLOROBENZYL)-1-(7H-PYRROLO(2,3-D)PYRIMIDIN- 4-YL)PIPERIDINE-4-CARBOXAMIDE BOUND TO PKB
Descriptor:RAC-BETA SERINE/THREONINE-PROTEIN KINASE, GLYCOGEN SYNTHASE KINASE-3 BETA, 4-AMINO-N-(4-CHLOROBENZYL)-1-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE
Authors:Davies, T.G., McHardy, T., Caldwell, J.J., Cheung, K.M., Hunter, L.J., Taylor, K., Rowlands, M., Ruddle, R., Henley, A., Brandon, A.D., Valenti, M., Fazal, L., Seavers, L., Raynaud, F.I., Eccles, S.A., Aherne, G.W., Garrett, M.D., Collins, I.
Deposit date:2010-01-22
Release date:2010-02-23
Last modified:2011-09-21
Method:X-RAY DIFFRACTION (1.93 Å)
Cite:Discovery of 4-Amino-1-(7H-Pyrrolo[2,3-D]Pyrimidin-4-Yl)Piperidine-4-Carboxamides as Selective, Orally Active Inhibitors of Protein Kinase B (Akt).
J.Med.Chem., 53, 2010
2XH5
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STRUCTURE OF 4-(4-TERT-BUTYLBENZYL)-1-(7H-PYRROLO(2,3-D)PYRIMIDIN-4- YL)PIPERIDIN-4-AMINE BOUND TO PKB
Descriptor:RAC-BETA SERINE/THREONINE-PROTEIN KINASE, GLYCOGEN SYNTHASE KINASE-3 BETA, 4-(4-tert-butylbenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-aminium
Authors:Davies, T.G., McHardy, T., Caldwell, J.J., Cheung, K.M., Hunter, L.J., Taylor, K., Rowlands, M., Ruddle, R., Henley, A., Brandon, A.D., Valenti, M., Fazal, L., Seavers, L., Raynaud, F.I., Eccles, S.A., Aherne, G.W., Garrett, M.D., Collins, I.
Deposit date:2010-06-09
Release date:2010-06-16
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.72 Å)
Cite:Discovery of 4-Amino-1-(7H-Pyrrolo[2,3-D]Pyrimidin-4-Yl)Piperidine-4-Carboxamides as Selective, Orally Active Inhibitors of Protein Kinase B (Akt).
J.Med.Chem., 53, 2010
2BRC
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STRUCTURE OF A HSP90 INHIBITOR BOUND TO THE N-TERMINUS OF YEAST HSP90.
Descriptor:ATP-DEPENDENT MOLECULAR CHAPERONE HSP82, 4-[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-METHYL-1H-PYRAZOL-5-YL]-6-ETHYLBENZENE-1,3-DIOL
Authors:Roe, S.M., Pearl, L.H., Prodromou, C.
Deposit date:2005-05-04
Release date:2005-09-29
Last modified:2018-02-28
Method:X-RAY DIFFRACTION (1.6 Å)
Cite:The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors.
Bioorg. Med. Chem. Lett., 15, 2005
2BRE
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STRUCTURE OF A HSP90 INHIBITOR BOUND TO THE N-TERMINUS OF YEAST HSP90.
Descriptor:ATP-DEPENDENT MOLECULAR CHAPERONE HSP82, 4-{4-[4-(3-AMINOPROPOXY)PHENYL]-1H-PYRAZOL-5-YL}-6-CHLOROBENZENE-1,3-DIOL
Authors:Roe, S.M., Pearl, L.H., Prodromou, C.
Deposit date:2005-05-04
Release date:2005-09-29
Last modified:2018-02-28
Method:X-RAY DIFFRACTION (2 Å)
Cite:The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors.
Bioorg. Med. Chem. Lett., 15, 2005
5AP6
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NATURALLY OCCURRING MUTATIONS IN THE MPS1 GENE PREDISPOSE CELLS TO KINASE INHIBITOR DRUG RESISTANCE.
Descriptor:DUAL SPECIFICITY PROTEIN KINASE TTK, ISOPROPYL 6-((4-(1,2-DIMETHYL-1H-IMIDAZOL-5-YL)PHENYL)AMINO)-2-(1-METHYL-1H-PYRAZOL-4-YL)-1H-PYRROLO[3,2-C]PYRIDINE-1-CARBOXYLATE, 1,2-ETHANEDIOL, ...
Authors:Gurden, M.D., Westwood, I.M., Faisal, A., Naud, S., Cheung, K.M., McAndrew, C., Wood, A., Schmitt, J., Boxall, K., Mak, G., Workman, P., Burke, R., Hoelder, S., Blagg, J., van Montfort, R., Linardopoulos, S.
Deposit date:2015-09-14
Release date:2015-09-23
Method:X-RAY DIFFRACTION (2.1 Å)
Cite:Naturally Occurring Mutations in the Mps1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance.
Cancer Res., 75, 2015
5AP7
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NATURALLY OCCURRING MUTATIONS IN THE MPS1 GENE PREDISPOSE CELLS TO KINASE INHIBITOR DRUG RESISTANCE.
Descriptor:MONOPOLAR SPINDLE KINASE 1, N-(2,6-DIETHYLPHENYL)-1-METHYL-8-({4-[(1-METHYLPIPERIDIN-4-YL)CARBAMOYL]-2-(TRIFLUOROMETHOXY)PHENYL}AMINO)-4,5-DIHYDRO-1H-PYRAZOLO[4,3-H]QUINAZOLINE-3-CARBOXAMIDE, 1,2-ETHANEDIOL, ...
Authors:Gurden, M.D., Westwood, I.M., Faisal, A., Naud, S., Cheung, K.M., McAndrew, C., Wood, A., Schmitt, J., Boxall, K., Mak, G., Workman, P., Burke, R., Hoelder, S., Blagg, J., van Montfort, R., Linardopoulos, S.
Deposit date:2015-09-14
Release date:2015-09-23
Method:X-RAY DIFFRACTION (2.45 Å)
Cite:Naturally Occurring Mutations in the Mps1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance.
Cancer Res., 75, 2015
5F4N
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MULTI-PARAMETER LEAD OPTIMIZATION TO GIVE AN ORAL CHK1 INHIBITOR CLINICAL CANDIDATE: (R)-5-((4-((MORPHOLIN-2-YLMETHYL)AMINO)-5-(TRIFLUOROMETHYL)PYRIDIN-2-YL)AMINO)PYRAZINE-2-CARBONITRILE (CCT245737)
Descriptor:Serine/threonine-protein kinase Chk1, methyl 6-[(5-cyanopyrazin-2-yl)amino]-4-[[(2~{R})-morpholin-2-yl]methylamino]pyridine-3-carboxylate, 1,2-ETHANEDIOL, ...
Authors:Collins, I., Garrett, M.D., van Montfort, R., Osborne, J.D., Matthews, T.P., McHardy, T., Proisy, N., Cheung, K.J., Lainchbury, M., Brown, N., Walton, M.I., Eve, P.D., Boxall, K.J., Hayes, A., Henley, A.T., Valenti, M.R., De Haven Brandon, A.K., Box, G., Westwood, I.M., Jamin, Y., Robinson, S.P., Leonard, P., Reader, J.C., Aherne, G.W., Raynaud, F.I., Eccles, S.A.
Deposit date:2015-12-03
Release date:2016-05-25
Last modified:2016-06-22
Method:X-RAY DIFFRACTION (1.91 Å)
Cite:Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).
J.Med.Chem., 59, 2016
2XK3
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 35
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[3-AMINO-6-(3-ETHYLTHIOPHEN-2-YL)PYRAZIN-2-YL]CYCLOHEXANE-1-CARBOXYLIC ACID, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.2 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XK4
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 17
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]-2-ethoxybenzoic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.1 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XK6
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 36
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, cis-4-[3-amino-6-(3-cyclopropylthiophen-2-yl)pyrazin-2-yl]cyclohexanecarboxylic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.2 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XK7
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 23
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, (3R,4R)-1-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]-3-ethylpiperidine-4-carboxylic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (1.992 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XK8
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 15
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]-2-methoxybenzoic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.001 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XKC
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 14
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]-2-methylbenzoic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.5 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XKD
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 12
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]benzoic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (1.96 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XKE
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STRUCTURE OF NEK2 BOUND TO AMINIPYRAZINE COMPOUND 5
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 1-[3-amino-6-(3-methoxyphenyl)pyrazin-2-yl]piperidine-4-carboxylic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-11-03
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.203 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
2XKF
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STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 2
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 1-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]piperidine-4-carboxylic acid, CHLORIDE ION
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2010-07-07
Release date:2010-10-27
Last modified:2011-07-13
Method:X-RAY DIFFRACTION (2.35 Å)
Cite:Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53, 2010
4A4X
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NEK2-EDE BOUND TO CCT248662
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-(2-AMINO-5-{4-[(DIMETHYLAMINO)METHYL]THIOPHEN-2-YL}PYRIDIN-3-YL)-2-{(1R)-1-[2-(TRIFLUOROMETHYL)PHENYL]ETHOXY}BENZAMIDE
Authors:Mas-Droux, C., Bayliss, R.
Deposit date:2011-10-20
Release date:2012-04-25
Method:X-RAY DIFFRACTION (2.4 Å)
Cite:Design of Potent and Selective Hybrid Inhibitors of the Mitotic Kinase Nek2: Structure-Activity Relationship, Structural Biology, and Cellular Activity.
J.Med.Chem., 55, 2012
4AFE
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NEK2 BOUND TO HYBRID COMPOUND 21
Descriptor:SERINE/THREONINE-PROTEIN KINASE NEK2, 4-(2-AMINO-5-{4-[(DIMETHYLAMINO)METHYL]THIOPHEN-2-YL}PYRIDIN-3-YL)-2-{[(1R,2Z)-4,4,4-TRIFLUORO-1-METHYLBUT-2-EN-1-YL]OXY}BENZAMIDE, 1,2-ETHANEDIOL
Authors:Yeoh, S., Innocenti, P., Hoelder, S., Bayliss, R.
Deposit date:2012-01-19
Release date:2012-04-25
Method:X-RAY DIFFRACTION (2.597 Å)
Cite:Design of Potent and Selective Hybrid Inhibitors of the Mitotic Kinase Nek2: Structure-Activity Relationship, Structural Biology, and Cellular Activity.
J.Med.Chem., 55, 2012