Search Results - "WARING, Michael J"

Defining optimum lipophilicity and molecular weight ranges for drug candidates―Molecular weight dependent lower logD limits based on permeability by WARING, Michael J

“…Analysis of a large, structurally diverse Caco-2 permeability dataset using a variety of statistical techniques suggests that logD and molecular weight are the…”
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An analysis of the attrition of drug candidates from four major pharmaceutical companies by Waring, Michael J., Arrowsmith, John, Leach, Andrew R., Leeson, Paul D., Mandrell, Sam, Owen, Robert M., Pairaudeau, Garry, Pennie, William D., Pickett, Stephen D., Wang, Jibo, Wallace, Owen, Weir, Alex

“…Key Points This Analysis article describes the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and…”
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FragLitesMinimal, Halogenated Fragments Displaying Pharmacophore Doublets. An Efficient Approach to Druggability Assessment and Hit Generation by Wood, Daniel J, Lopez-Fernandez, J. Daniel, Knight, Leanne E, Al-Khawaldeh, Islam, Gai, Conghao, Lin, Shengying, Martin, Mathew P, Miller, Duncan C, Cano, Céline, Endicott, Jane A, Hardcastle, Ian R, Noble, Martin E. M, Waring, Michael J

“…Identifying ligand binding sites on proteins is a critical step in target-based drug discovery. Current approaches to this require resource-intensive screening…”
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AZD5153: A Novel Bivalent BET Bromodomain Inhibitor Highly Active against Hematologic Malignancies by Rhyasen, Garrett W, Hattersley, Maureen M, Yao, Yi, Dulak, Austin, Wang, Wenxian, Petteruti, Philip, Dale, Ian L, Boiko, Scott, Cheung, Tony, Zhang, Jingwen, Wen, Shenghua, Castriotta, Lillian, Lawson, Deborah, Collins, Michael, Bao, Larry, Ahdesmaki, Miika J, Walker, Graeme, O'Connor, Greg, Yeh, Tammie C, Rabow, Alfred A, Dry, Jonathan R, Reimer, Corinne, Lyne, Paul, Mills, Gordon B, Fawell, Stephen E, Waring, Michael J, Zinda, Michael, Clark, Edwin, Chen, Huawei

“…The bromodomain and extraterminal (BET) protein BRD4 regulates gene expression via recruitment of transcriptional regulatory complexes to acetylated chromatin…”
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Potent and selective bivalent inhibitors of BET bromodomains by Waring, Michael J, Chen, Huawei, Rabow, Alfred A, Walker, Graeme, Bobby, Romel, Boiko, Scott, Bradbury, Rob H, Callis, Rowena, Clark, Edwin, Dale, Ian, Daniels, Danette L, Dulak, Austin, Flavell, Liz, Holdgate, Geoff, Jowitt, Thomas A, Kikhney, Alexey, McAlister, Mark, Méndez, Jacqui, Ogg, Derek, Patel, Joe, Petteruti, Philip, Robb, Graeme R, Robers, Matthew B, Saif, Sakina, Stratton, Natalie, Svergun, Dmitri I, Wang, Wenxian, Whittaker, David, Wilson, David M, Yao, Yi

“…Structural insights demonstrating small-molecule-mediated dimerization of BRD4 bromodomains led to the development of biBET, a compound that potently inhibits…”
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A quantitative assessment of hERG liability as a function of lipophilicity by Waring, Michael J., Johnstone, Craig

“…The impact of lipophilicity as a factor contributing to hERG potency is assessed for a large dataset of compounds of differing ionisation type. This dataset is…”
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Using diagrams to support the research process: examples from grounded theory by Buckley, Charles A, Waring, Michael J

“…Despite their potential for yielding an understanding of the conceptualisation being developed, diagrams remain one of the least utilised tools in the…”
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A genetically selected cyclic peptide inhibitor of BCL6 homodimerization by Osher, Eliot L., Castillo, Francisco, Elumalai, Nagarajan, Waring, Michael J., Pairaudeau, Garry, Tavassoli, Ali

“…[Display omitted] We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS…”
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Optimization of a Series of Bivalent Triazolopyridazine Based Bromodomain and Extraterminal Inhibitors: The Discovery of (3R)‑4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3‑b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one (AZD5153) by Bradbury, Robert H, Callis, Rowena, Carr, Gregory R, Chen, Huawei, Clark, Edwin, Feron, Lyman, Glossop, Steve, Graham, Mark A, Hattersley, Maureen, Jones, Chris, Lamont, Scott G, Ouvry, Gilles, Patel, Anil, Patel, Joe, Rabow, Alfred A, Roberts, Craig A, Stokes, Stephen, Stratton, Natalie, Walker, Graeme E, Ward, Lara, Whalley, David, Whittaker, David, Wrigley, Gail, Waring, Michael J

“…Here we report the discovery and optimization of a series of bivalent bromodomain and extraterminal inhibitors. Starting with the observation of BRD4 activity…”
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Pharmacological effectors of GRP78 chaperone in cancers by Bailly, Christian, Waring, Michael J.

“…[Display omitted] The protein chaperone GRP78 is a master regulator of endoplasmic reticulum (ER) functions and is frequently over-expressed at the surface of…”
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Defining optimum lipophilicity and molecular weight ranges for drug candidates—Molecular weight dependent lower log D limits based on permeability by Waring, Michael J.

“…Analysis of a large, structurally diverse Caco-2 permeability dataset using a variety of statistical techniques suggests that log D and molecular weight are…”
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Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding by Naidu, Mamta D, Agarwal, Rakhi, Pena, Louis A, Cunha, Luis, Mezei, Mihaly, Shen, Min, Wilson, 3rd, David M, Liu, Yuan, Sanchez, Zina, Chaudhary, Pankaj, Wilson, Samuel H, Waring, Michael J

“…Lucanthone and hycanthone are thioxanthenone DNA intercalators used in the 1980s as antitumor agents. Lucanthone is in Phase I clinical trial, whereas…”
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CoII(Chromomycin)2 Complex Induces a Conformational Change of CCG Repeats from i-Motif to Base-Extruded DNA Duplex by Chen, Yu-Wen, Satange, Roshan, Wu, Pei-Ching, Jhan, Cyong-Ru, Chang, Chung-ke, Chung, Kuang-Ren, Waring, Michael, Lin, Sheng-Wei, Hsieh, Li-Ching, Hou, Ming-Hon

“…We have reported the propensity of a DNA sequence containing CCG repeats to form a stable i-motif tetraplex structure in the absence of ligands. Here we show…”
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The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold by Bonn, Peter, Brink, D. Mikael, Fägerhag, Jonas, Jurva, Ulrik, Robb, Graeme R., Schnecke, Volker, Svensson Henriksson, Anette, Waring, Michael J., Westerlund, Christer

“…Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK…”
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Practical application of ligand efficiency metrics in lead optimisation by Scott, James S., Waring, Michael J.

“…[Display omitted] The use of composite metrics that normalise biological potency values in relation to markers of physicochemical properties, such as size or…”
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Micellar Buchwald–Hartwig Coupling of Aryl and Heteroarylamines for the Synthesis of DNA-Encoded Libraries by Graham, Jessica S, Hunter, James H, Waring, Michael J

“…DNA-encoded libraries are a very efficient means of identifying ligands for protein targets in high throughput. To fully maximize their use, it is essential to…”
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Development of a Micellar-Promoted Heck Reaction for the Synthesis of DNA-Encoded Libraries by Stanway-Gordon, Harriet A., Odger, Jake A., Waring, Michael J.

“…The capability of DNA encoded libraries (DELs) as a method of small molecule hit identification is becoming widely established in drug discovery. While their…”
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High Fidelity Suzuki–Miyaura Coupling for the Synthesis of DNA Encoded Libraries Enabled by Micelle Forming Surfactants by Hunter, James H, Prendergast, Lisa, Valente, Louis F, Madin, Andrew, Pairaudeau, Garry, Waring, Michael J

“…DNA encoded chemical libraries provide a highly efficient means of screening vast numbers of small molecules against an immobilized protein target. Their…”
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Directed Dihydroxylation of Cyclic Allylic Alcohols and Trichloroacetamides Using OsO4/TMEDA by Donohoe, Timothy J, Blades, Kevin, Moore, Peter R, Waring, Michael J, Winter, Jon J. G, Helliwell, Madeleine, Newcombe, Nicholas J, Stemp, Geoffrey

“…The oxidation of a range of cyclic allylic alcohols and amides with OsO4/TMEDA is presented. Under these conditions, hydrogen bonding control leads to the…”
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On‐DNA Transfer Hydrogenolysis and Hydrogenation for the Synthesis of DNA‐Encoded Chemical Libraries by Stanway‐Gordon, Harriet A., Graham, Jessica S., Waring, Michael J.

“…DNA‐encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on…”
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