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Your search keyword '"James Brooke Murray"' showing total 3 results
Start Over Author "James Brooke Murray" Journal bioorganic & medicinal chemistry letters
3 results on '"James Brooke Murray"'

1. Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution

Author

David A. Robinson, Claire L. Nunns, Christopher J. Northfield, Jonathan D. Moore, Christine M. Richardson, Ben Davis, James Brooke Murray, Victoria Oldfield, Pawel Dokurno, Simon F. Scrace, Lisa Baker, Stuart C. Ray, Christophe Fromont, Allan E. Surgenor, Natalia Matossova, Andrew John Potter, and Christopher J. Bryant

Subjects
Models, Molecular, Stereochemistry, Clinical Biochemistry, Cell, Pharmaceutical Science, Isomerase, Biochemistry, chemistry.chemical_compound, Drug Discovery, medicine, Humans, Imidazole, Threonine, NIMA-Interacting Peptidylprolyl Isomerase, Molecular Biology, Molecular Structure, Kinase, Drug discovery, Organic Chemistry, Imidazoles, Peptidylprolyl Isomerase, medicine.anatomical_structure, chemistry, PIN1, Molecular Medicine, Caco-2 Cells
Abstract

Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.

Published
2010

2. Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping

Author

Philip Stephen Jackson, Douglas S. Williamson, Martin J. Drysdale, Claire L. Nunns, Roderick E. Hubbard, Rob Howes, Harry Finch, Peter Kierstan, Martin J. Parratt, Jonathan D. Moore, Allan E. Surgenor, Heather Simmonite, Christopher J. Torrance, Georg Lentzen, Christine M. Richardson, Jenifer Borgognoni, Pawel Dokurno, and James Brooke Murray

Subjects
Virtual screening, biology, Molecular model, Chemistry, Stereochemistry, Cyclin-Dependent Kinase 2, Organic Chemistry, Clinical Biochemistry, Cyclin-dependent kinase 2, Rational design, Pharmaceutical Science, Crystal structure, Crystallography, X-Ray, Biochemistry, Cyclin-dependent kinase, Docking (molecular), Drug Design, Drug Discovery, biology.protein, Molecular Medicine, Kinase binding, Protein Kinase Inhibitors, Molecular Biology
Abstract

Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.

Published
2007

3. Corrigendum to 'Structure-guided design of α-amino acid-derived Pin1 inhibitors' [Bioorg. Med. Chem. Lett. 20 (2010) 586]

Author

Claire L. Nunns, Jonathan D. Moore, Simon F. Scrace, David A. Robinson, Lisa Baker, Pawel Dokurno, James Brooke Murray, Natalia Matassova, Louisa Gueritz, Andrew J. Potter, Stuart C. Ray, Christine M. Richardson, Ben Davis, Christopher J. Bryant, and Allan E. Surgenor

Subjects
chemistry.chemical_classification, chemistry, Stereochemistry, Organic Chemistry, Clinical Biochemistry, Drug Discovery, PIN1, Pharmaceutical Science, Molecular Medicine, Molecular Biology, Biochemistry, Amino acid
Published
2010

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