Browsing by Author "McInnes, C."
Now showing items 1-11 of 11
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Catch the kinase conformer
McInnes, C.; Mezna, M.; Kontopidis, G. (2006)Protein kinases exist in inactive and active states, but little attention has been paid to which state is or should be the target in drug discovery efforts. In this issue of Chemistry & Biology, Okram et al. [1] tackle ... -
Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5- dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors
McIntyre, N. A.; McInnes, C.; Griffiths, G.; Barnett, A. L.; Kontopidis, G.; Slawin, A. M. Z.; Jackson, W.; Thomas, M.; Zheleva, D. I.; Wang, S.; Blake, D. G.; Westwood, N. J.; Fischer, P. M. (2010)Following the recent discovery and development of 2-anilino-4-(thiazol-5- yl)pyrimidine cyclin dependent kinase (CDK) inhibitors, a program was initiated to evaluate related ring-constrained analogues, specifically, 2-methyl- ... -
Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents
Wang, S.; Griffiths, G.; Midgley, C. A.; Barnett, A. L.; Cooper, M.; Grabarek, J.; Ingram, L.; Jackson, W.; Kontopidis, G.; McClue, S. J.; McInnes, C.; McLachlan, J.; Meades, C.; Mezna, M.; Stuart, I.; Thomas, M. P.; Zheleva, D. I.; Lane, D. P.; Jackson, R. C.; Glover, D. M.; Blake, D. G.; Fischer, P. M. (2010)The main difficulty in the development of ATP antagonist kinase inhibitors is target specificity, since the ATP-binding motif is present in many proteins. We introduce a strategy that has allowed us to identify compounds ... -
Discovery of N-Phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors
Wang, S.; Midgley, C. A.; Scaërou, F.; Grabarek, J. B.; Griffiths, G.; Jackson, W.; Kontopidis, G.; McClue, S. J.; McInnes, C.; Meades, C.; Mezna, M.; Plater, A.; Stuart, I.; Thomas, M. P.; Wood, G.; Clarke, R. G.; Blake, D. G.; Zheleva, D. I.; Lane, D. P.; Jackson, R. C.; Glover, D. M.; Fischer, P. M. (2010)Through cell-based screening of our kinase-directed compound collection, we discovered that a subset of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amines were potent cytotoxic agents against cancer cell lines, suppressed mitotic ... -
Efficient soluble expression of active recombinant human cyclin A2 mediated by E. coli molecular chaperones
Grigoroudis, A. I.; McInnes, C.; Premnath, P. N.; Kontopidis, G. (2015)Bacterial expression of human proteins continues to present a critical challenge in protein crystallography and drug design. While human cyclin A constructs have been extensively characterized in complex with cyclin dependent ... -
Iterative Conversion of Cyclin Binding Groove Peptides into Drug like CDK Inhibitors with Antitumor Activity
Premnath, P. N.; Craig, S. N.; Liu, S.; Anderson, E. L.; Grigoroudis, A. I.; Kontopidis, G.; Perkins, T. L.; Wyatt, M. D.; Pittman, D. L.; McInnes, C. (2015)The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive ... -
Optimization of Non-ATP Competitive CDK/Cyclin Groove Inhibitors through REPLACE-Mediated Fragment Assembly
Liu, S.; Premnath, P. N.; Bolger, J. K.; Perkins, T. L.; Kirkland, L. O.; Kontopidis, G.; McInnes, C. (2013)A major challenge in drug discovery is to develop and improve methods for targeting protein-protein interactions. Further exemplification of the REPLACE (REplacement with Partial Ligand Alternatives through Computational ... -
Quantification of the Effects of Ionic Strength, Viscosity, and Hydrophobicity on Protein-Ligand Binding Affinity
Papaneophytou, C. P.; Grigoroudis, A. I.; McInnes, C.; Kontopidis, G. (2014)In order to quantify the interactions between molecules of biological interest, the determination of the dissociation constant (K-d) is essential. Estimation of the binding affinity in this way is routinely performed in ... -
REPLACE: A strategy for iterative design of cyclin-binding groove inhibitors
Andrews, M. J. I.; Kontopidis, G.; McInnes, C.; Plater, A.; Innes, L.; Cowan, A.; Jewsbury, P.; Fischer, P. M. (2006)We describe a drug-design strategy termed REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) in which nonpeptidic surrogates for specific determinants of known peptide ligands are ... -
Targeting active and inactive CDK2 differential binding inhibitors
Kontopidis, G.; McInnes, C.; Pandalaneni, S.; McNae, I.; Gibson, D.; Mezna, M.; Thomas, M.; Wood, G.; Wang, S.; Walkinshaw, M.; Fischer, P. (2008) -
Truncation and optimisation of peptide inhibitors of cyclin-dependent kinase 2-cyclin A through structure-guided design
Kontopidis, G.; Andrews, M. J.; McInnes, C.; Plater, A.; Innes, L.; Renachowski, S.; Cowan, A.; Fischer, P. M. (2009)The cyclin-dependent kinase 2-cyclin A complex is an important regulator of the DNA-synthesis phase of the mammalian cell cycle, which is frequently deregulated in cancer. Rather than blocking the ATP-binding site of the ...