Search Results - "Holdgate, A."

Mechanistic enzymology in drug discovery: a fresh perspective by Holdgate, Geoffrey A., Meek, Thomas D., Grimley, Rachel L.

“…Key Points The application of detailed mechanistic enzyme kinetics is vital for the characterization of enzyme targets; furthermore, it is crucial to aid in…”
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A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators by Angus, D. C., Barnato, A. E., Bell, D., Bellomo, R., Chong, C.-R., Coats, T. J., Davies, A., Delaney, A., Harrison, D. A., Holdgate, A., Howe, B., Huang, D. T., Iwashyna, T., Kellum, J. A., Peake, S. L., Pike, F., Reade, M. C., Rowan, K. M., Singer, M., Webb, S. A. R., Weissfeld, L. A., Yealy, D. M., Young, J. D.

“…Purpose To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the…”
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Measurements of binding thermodynamics in drug discovery by Holdgate, Geoffrey A., Ward, Walter H.J.

“…Improved methods are now available to characterize binding thermodynamics. This review summarizes these methods and the exploitation of the derived…”
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A perspective on the discovery of enzyme activators by Turberville, Antonia, Semple, Hannah, Davies, Gareth, Ivanov, Delyan, Holdgate, Geoffrey A.

“…Enzyme activation remains a largely under-represented and poorly exploited area of drug discovery despite some key literature examples of the successful…”
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Characterisation of high throughput screening outputs for small molecule degrader discovery by Bell, Lillie E., Bardelle, Catherine, Packer, Martin J, Kastl, Johanna, Holdgate, Geoffrey A., Davies, Gareth

“…Targeted protein degradation is an important mechanism carried out by the cellular machinery, one that is gaining momentum as an exploitable strategy for the…”
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POLARISED views and FRETting about probe modulation assays: Learning from High Throughput Screening by Lanne, Alice, Bardelle, Catherine, Davies, Gareth, Turberville, Antonia, Semple, Hannah, Moore, Rachel, Holdgate, Geoffrey A.

“…Fluorescent probe modulation assays are a widely used approach to monitor displacement or stabilisation of fluorescently labelled tool ligands by test…”
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Screening for molecular glues – Challenges and opportunities by Holdgate, Geoffrey A., Bardelle, Catherine, Berry, Sophia K., Lanne, Alice, Cuomo, Maria Emanuela

“…Molecular glues are small molecules, typically smaller than PROTACs, and usually with improved physicochemical properties that aim to stabilise the interaction…”
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Utilising acoustic mist ionisation mass spectrometry to identify redox cycling compounds in high throughput screening outputs by Moore, Rachel, Molyneux, Corinne, Sinclair, Ian, Holdgate, Geoffrey A., Walsh, Jarrod

“…Rapid triage of compounds acting via undesired mechanisms is a crucial stage in a high-throughput screening (HTS) cascade to ensure time and resource is…”
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High-throughput detection of metal contamination in HTS outputs by Molyneux, Corinne, Sinclair, Ian, Lightfoot, Helen L., Walsh, Jarrod, Holdgate, Geoffrey A., Moore, Rachel

“…Large compound libraries utilised for HTS often include metal contaminated compounds which can interfere with assay signal or target biology, and therefore…”
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Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530 by Green, Tim P., Fennell, Mike, Whittaker, Robin, Curwen, Jon, Jacobs, Vivien, Allen, Jack, Logie, Armelle, Hargreaves, Judith, Hickinson, D. Mark, Wilkinson, Robert W., Elvin, Paul, Boyer, Brigitte, Carragher, Neil, Plé, Patrick A., Bermingham, Alun, Holdgate, Geoffrey A., Ward, Walter H.J., Hennequin, Laurent F., Davies, Barry R., Costello, Gerard F.

“…AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and anti-invasive effects in vitro, and inhibited metastasis in a murine model of…”
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High throughput screening of 0.5 million compounds against CRAF using Alpha CETSA by Rowlands, Hannah, Tschapalda, Kirsten, Blackett, Carolyn, Ivanov, Delyan, Plant, Darren, Shaw, Joseph, Thomas, Andrew, Packer, Martin, Arnold, Laurence, Holdgate, Geoffrey A.

“…The cellular thermal shift assay (CETSA®) has increasingly been used in early drug discovery to provide a measure of cellular target engagement. Traditionally,…”
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Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic by Holdgate, A, Pollock, T

“…Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the…”
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Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic by Holdgate, A, Pollock, T

“…Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the…”
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Making cool drugs hot: isothermal titration calorimetry as a tool to study binding energetics by Holdgate, G A

“…Characterization of the thermodynamics of binding interactions is important in improving our understanding of bimolecular recognition and forms an essential…”
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A comparison of tape-tying versus a tube-holding device for securing endotracheal tubes in adults by MURDOCH, E, HOLDGATE, A

“…During the transfer of intubated patients, endotracheal tube security is paramount. This study aims to compare two methods of securing an endotracheal tube in…”
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Kinetic and Structural Characteristics of the Inhibition of Enoyl (Acyl Carrier Protein) Reductase by Triclosan by Ward, Walter H. J, Holdgate, Geoffrey A, Rowsell, Siân, McLean, Estelle G, Pauptit, Richard A, Clayton, Edward, Nichols, Wright W, Colls, Jeremy G, Minshull, Claire A, Jude, David A, Mistry, Anil, Timms, David, Camble, Roger, Hales, Neil J, Britton, Carolyn J, Taylor, Ian W. F

“…Triclosan is used widely as an antibacterial agent in dermatological products, mouthwashes, and toothpastes. Recent studies imply that antibacterial activity…”
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Drug discovery for epigenetics targets by Holdgate, Geoffrey A, Bardelle, Catherine, Lanne, Alice, Read, Jon, O'Donovan, Daniel H, Smith, James M, Selmi, Nidhal, Sheppard, Robert

“…Dysregulation of the epigenome is associated with the onset and progression of several diseases, including cancer, autoimmune, cardiovascular, and neurological…”
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Bromodomain Interactions with Acetylated Histone 4 Peptides in the BRD4 Tandem Domain: Effects on Domain Dynamics and Internal Flexibility by Wernersson, Sven, Bobby, Romel, Flavell, Liz, Milbradt, Alexander G., Holdgate, Geoffrey A., Embrey, Kevin J., Akke, Mikael

“…The bromodomain and extra-terminal (BET) protein BRD4 regulates gene expression via recruitment of transcriptional regulatory complexes to acetylated…”
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Advancing automation in high-throughput screening: Modular unguarded systems enable adaptable drug discovery by Hansel, Catherine S., Plant, Darren L., Holdgate, Geoffrey A., Collier, Matthew J., Plant, Helen

“…•Automation is critical in delivering adaptable, robust and reproducible high-throughput screens.•Innovative design solutions have delivered increased…”
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The Entropic Penalty of Ordered Water Accounts for Weaker Binding of the Antibiotic Novobiocin to a Resistant Mutant of DNA Gyrase:  A Thermodynamic and Crystallographic Study by Holdgate, Geoffrey A, Tunnicliffe, Alan, Ward, Walter H. J, Weston, Simon A, Rosenbrock, Gina, Barth, Peter T, Taylor, Ian W. F, Pauptit, Richard A, Timms, David

“…Novobiocin is an antibiotic which binds to a 24 kDa fragment from the B subunit of DNA gyrase. Naturally occurring resistance arises from mutation of Arg-136…”
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