Phenotypic screening identifies a trisubstituted imidazo[1,2-a]pyridine series that induces differentiation in multiple AML cell lines. Laia Josa-Culleré, Sébastien R.G. Galan, Thomas J. Cogswell, Thomas R. Jackson, Morgan Jay-Smith, Laura Mola, Christopher R. Greaves, Tom S. Carter, Katrina S. Madden, Sophie Trott, Douzi Zhang, Carole J.R. Bataille, Stephen G. Davies, Paresh Vyas, Thomas A. Milne, Alan Naylor, Graham M. Wynne, Angela J. Russell. Eur J Med Chem 2023, in press, 115509  https://doi.org/10.1016/j.ejmech.2023.115509

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A tubulin binding molecule drives differentiation of acute myeloid leukemia cells. Thomas R Jackson, Aini Vuorinen, Laia Josa-Culleré, Katrina S Madden, Daniel Conole, Thomas J Cogswell, Isabel V L Wilkinson, Laura M Kettyle, Douzi Zhang, Alison O'Mahony, Deanne Gracias, Lorna McCall, Robert Westwood, Georg C Terstappen, Stephen G Davies, Edward W Tate, Graham M Wynne, Paresh Vyas, Angela J Russell, Thomas A Milne. iScience. 2022, 25(8), 104787 https://doi.org/10.1016/j.isci.2022.104787

 

Structure-activity relationships of 2-pyrimidinecarbohydrazides as utrophin modulators for the potential treatment of Duchenne muscular dystrophy. Maria Chatzopoulou, Daniel Conole, Enrico Emer, Jessica A. Rowley, Nicky J. Willis, Sarah E. Squire, Becky Gill, Steve Brough, Francis X. Wilson, Graham M. Wynne, Stephen G. Davies, Kay E. Davies, Angela J. Russell. Bioorg Med Chem. 2022, 69, 116812 https://doi.org/10.1016/j.bmc.2022.116812

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Pilot Study to Quantify Palladium Impurities in Lead-like Compounds Following Commonly Used Purification Techniques. Maria Chatzopoulou, Katrina S. Madden, Liam J. Bromhead, Christopher Greaves, Thomas J. Cogswell, Solange Da Silva Pinto, Sebastien R. G. Galan, Irene Georgiou, Matthew S. Kennedy, Alice Kennett, Geraint Apps, Angela J. Russell, Graham M. Wynne. ACS Med Chem Lett 2022, 13(2), 262,  https://doi.org/10.1021/acsmedchemlett.1c00638

 

Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro. Laia Josa-Culleré, Thomas J. Cogswell, Irene Georgiou, Morgan Jay-Smith, Thomas R. Jackson, Carole J. R. Bataille, Stephen G. Davies, Paresh Vyas, Thomas A. Milne, Graham M. Wynne, Angela J. Russell. Molecules 2021, 26(21), 6648; https://doi.org/10.3390/molecules26216648

 

A Phenotypic Screen Identifies a Compound Series That Induces Differentiation of Acute Myeloid Leukemia Cells In Vitro and Shows Antitumor Effects In Vivo. Laia Josa-Culleré, Katrina S Madden, Thomas J Cogswell, Thomas R Jackson, Tom S Carter, Douzi Zhang, Graham Trevitt, Stephen G Davies, Paresh Vyas, Graham M Wynne, Thomas A Milne, Angela J Russell. J Med Chem 2021, 64(21), 15608–15628 https://doi.org/10.1021/acs.jmedchem.1c00574

 

Discovery and mechanism of action studies of 4,6-diphenylpyrimidine-2-carbohydrazides as utrophin modulators for the treatment of Duchenne muscular dystrophy. Aini Vuorinen, Isabel V L Wilkinson, Maria Chatzopoulou, Ben Edwards, Sarah E Squire, Rebecca J Fairclough, Noelia Araujo Bazan, Josh A Milner, Daniel Conole, James R Donald, Nandini Shah, Nicky J Willis, R Fernando Martínez, Francis X Wilson, Graham M Wynne, Stephen G Davies, Kay E Davies, Angela J Russell. Eur J Med Chem 2021, 220, 113431 https://doi.org/10.1016/j.ejmech.2021.113431

 

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni. Frederick A Partridge, Carole J R Bataille, Ruth Forman, Amy E Marriott, Josephine Forde-Thomas, Cécile Häberli, Ria L Dinsdale, James D B O'Sullivan, Nicky J Willis, Graham M Wynne, Helen Whiteland, John Archer, Andrew Steven, Jennifer Keiser, Joseph D Turner, Karl F Hoffmann, Mark J Taylor, Kathryn J Else, Angela J Russell, David B Sattelle. ACS Infect Dis 2021, 7(5), 1260-1274 https://doi.org/10.1021/acsinfecdis.1c00025

 

Decreasing HepG2 Cytotoxicity by Lowering the Lipophilicity of Benzo[d]oxazolephosphinate Ester Utrophin Modulators. Maria Chatzopoulou, Enrico Emer, Cristina Lecci, Jessica A Rowley, Anne-Sophie Casagrande, Lee Moir, Sarah E Squire, Stephen G Davies, Shawn Harriman, Graham M Wynne, Francis X Wilson, Kay E Davies, Angela J Russell. ACS Med Chem Lett 2020, 11(12), 2421-2427 https://doi.org/10.1021/acsmedchemlett.0c00405

 

Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family. Camilo E Quevedo, Carole J R Bataille, Simon Byrne, Matthew Durbin, Jon Elkins, Abigail Guillermo, Alan M Jones, Stefan Knapp, Anna Nadali, Roderick G Walker, Isabel V L Wilkinson, Graham M Wynne, Stephen G Davies, Angela J Russell. Bioorg Med Chem 2020, 28(22), 115724 https://doi.org/10.1016/j.bmc.2020.115724

 

The BET inhibitor CPI203 promotes ex vivo expansion of cord blood long-term repopulating HSCs and megakaryocytes. Peng Hua, Joanna Hester, George Adigbli, Rong Li, Bethan Psaila, Anindita Roy, Carole J R Bataille, Graham M Wynne, Thomas Jackson, Thomas A Milne, Angela J Russell, James Davies, Irene Roberts, Fadi Issa, Suzanne M Watt. Blood 2020, 136(21), 2410-2415 https://doi.org/10.1182/blood.2020005357

 

2-Arylbenzo[ d]oxazole Phosphinate Esters as Second-Generation Modulators of Utrophin for the Treatment of Duchenne Muscular Dystrophy. Arran Babbs, Adam Berg, Maria Chatzopoulou, Kay E Davies, Stephen G Davies, Benjamin Edwards, David J Elsey, Enrico Emer, Simon Guiraud, Shawn Harriman, Cristina Lecci, Lee Moir, David Peters, Neil Robinson, Jessica A Rowley, Angela J Russell, Sarah E Squire, Jonathon M Tinsley, Francis X Wilson, Graham M Wynne. J Med Chem 2020, 63(14), 7880-7891 https://doi.org/10.1021/acs.jmedchem.0c00807

 

Anthelmintic drug discovery: target identification, screening methods and the role of open science. Frederick A Partridge, Ruth Forman, Carole J R Bataille, Graham M Wynne, Marina Nick, Angela J Russell, Kathryn J Else, David B Sattelle. Beilstein J Org Chem 2020, 16, 1203-1224 https://doi.org/10.3762/bjoc.16.105

 

Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid. Isabel V L Wilkinson, Kelly J Perkins, Hannah Dugdale, Lee Moir, Aini Vuorinen, Maria Chatzopoulou, Sarah E Squire, Sebastian Monecke, Alexander Lomow, Marcus Geese, Philip D Charles, Peter Burch, Jonathan M Tinsley, Graham M Wynne, Stephen G Davies, Francis X Wilson, Fraydoon Rastinejad, Shabaz Mohammed, Kay E Davies, Angela J Russell. Angew Chem Int Ed Engl 2020, 59(6), 2420-2428

 https://doi.org/10.1002/anie.201912392

 

From diagnosis to therapy in Duchenne muscular dystrophy. Arran Babbs, Maria Chatzopoulou, Ben Edwards, Sarah E Squire, Isabel V L Wilkinson, Graham M Wynne, Angela J Russell, Kay E Davies. Biochem Soc Trans 2020, 48(3), 813-821 https://doi.org/10.1042/bst20190282

 

Synthesis of SMT022357 enantiomers and in vivo evaluation in a Duchenne muscular dystrophy mouse model. Arran Babbs, Adam Berg, Maria Chatzopoulou, Kay E.Davies, Stephen G.Davies, Benjamin Edwards, David J.Elsey, Enrico Emer, Aude L.A.Figuccia, Ai M.Fletcher, Simon Guiraud, Shawn Harriman, Lee Moir, Neil Robinson, Jessica A.Rowley, Angela J.Russell, Sarah E.Squire, James E.Thomson, Jonathon M.Tinsley, Francis X.Wilson, Graham M.Wynne Tetrahedron 2020, 76(2), 130819 https://doi.org/10.1016/j.tet.2019.130819

 

Characterisation of utrophin modulator SMT C1100 as a non-competitive inhibitor of firefly luciferase. Wilkinson IVL, Reynolds JK, Galan SRG, Vuorinen A, Sills AJ, Pires E, Wynne GM, Wilson FX, Russell AJ. Bioorg Chem. 2020, 94, 103395 https://doi.org/10.1016/j.bioorg.2019.103395

 

Isolation, Structural Identification, Synthesis, and Pharmacological Profiling of 1,2-trans-Dihydro-1,2-diol Metabolites of the Utrophin Modulator Ezutromid. Chatzopoulou M, Claridge TDW, Davies KE, Davies SG, Elsey DJ, Emer E, Fletcher AM, Harriman S, Robinson N, Rowley JA, Russell AJ, Tinsley JM, Weaver R, Wilkinson IVL, Willis NJ, Wilson FX, Wynne GM. J Med Chem. 2020, 63(5), 2547-2556 https://doi.org/10.1021/acs.jmedchem.9b01547 

 

A Biased Agonist at Immunometabolic Receptor GPR84 Causes Distinct Functional Effects in Macrophages. Lucy D, Purvis GSD, Zeboudj L, Chatzopoulou M, Recio C, Bataille CJR, Wynne GM, Greaves DR, Russell AJ. ACS Chem Biol. 2019, 14(9), 2055-2064 https://doi.org/10.1021/acschembio.9b00533

 

Chemical Instability and Promiscuity of Arylmethylidenepyrazolinone-Based MDMX Inhibitors. Stefaniak J, Lewis AM, Conole D, Galan SRG, Bataille CJR, Wynne GM, Castaldi MP, Lundbäck T, Russell AJ, Huber KVM. ACS Chem Biol. 2018, 13(10), 2849-2854 https://doi.org/10.1021/acschembio.8b00665

 

2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm  Partridge FA, Forman R, Willis NJ, Bataille CJR, Murphy EA, Brown AE, Heyer-Chauhan N, Marinič B, Sowood DJC, Wynne GM, Else KJ, Russell AJ, Sattelle DB. PLoS Negl Trop Dis. 2018, 12(7), e0006487 https://doi.org/10.1371/journal.pntd.0006487

 

Activation of the Immune-Metabolic Receptor GPR84 Enhances Inflammation and Phagocytosis in Macrophages. Recio C, Lucy D, Purvis GSD, Iveson P, Zeboudj L, Iqbal AJ, Lin D, O'Callaghan C, Davison L, Griesbach E, Russell AJ, Wynne GM, Dib L, Monaco C, Greaves DR. Front Immunol. 2018, 9, 1419 https://doi.org/10.3389/fimmu.2018.01419

 

An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes. Partridge FA, Brown AE, Buckingham SD, Willis NJ, Wynne GM, Forman R, Else KJ, Morrison AA, Matthews JB, Russell AJ, Lomas DA, Sattelle DB. Int J Parasitol Drugs Drug Resist. 2018, 8(1), 8-21 https://doi.org/10.1016/j.ijpddr.2017.11.004

 

The Role of Metabolite-Sensing G Protein-Coupled Receptors in Inflammation and Metabolic Disease. Recio C, Lucy D, Iveson P, Iqbal AJ, Valaris S, Wynne G, Russell AJ, Choudhury RP, O'Callaghan C, Monaco C, Greaves DR. Antioxid Redox Signal. 2018, 29(3), 237-256 https://doi.org/10.1089/ars.2017.7168

 

Efficacy of a series of alpha-pyrone derivatives against Leishmania (L.) infantum and Trypanosoma cruzi. Tempone AG, Ferreira DD, Lima ML, Costa Silva TA, Borborema SET, Reimão JQ, Galuppo MK, Guerra JM, Russell AJ, Wynne GM, Lai RYL, Cadelis MM, Copp BR. Eur J Med Chem. 2017, 139, 947-960 https://doi.org/10.1016/j.ejmech.2017.08.055

 

A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor. Kerr AG, Tam LCS, Hale AB, Cioroch M, Douglas G, Agkatsev S, Hibbitt O, Mason J, Holt-Martyn J, Bataille CJR, Wynne GM, Channon KM, Russell AJ, Wade-Martins R. J Pharmacol Exp Ther. 2017, 361(3), 417-428 https://doi.org/10.1124/jpet.116.239574

 

Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. Bataille CJ, Brennan MB, Byrne S, Davies SG, Durbin M, Fedorov O, Huber KV, Jones AM, Knapp S, Liu G, Nadali A, Quevedo CE, Russell AJ, Walker RG, Westwood R, Wynne GM. Bioorg Med Chem. 2017, 25(9),2657-2665 https://doi.org/10.1016/j.bmc.2017.02.056

 

Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo, Frederick A Partridge; Emma A Murphy; Nicky J Willis; Carole JR Bataille; Ruth Forman; Narinder Heyer-Chauhan; Bruno Marinič; Daniel JC Sowood; Graham M Wynne; Kathryn J Else; Angela J Russell; David Sattelle; PLOS Neglected Tropical Diseases Partridge FA, Murphy EA, Willis NJ, Bataille CJR, Forman R, Heyer-Chauhan N, et al. (2017) Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo. PLoS Negl Trop Dis 2017, 11(2): e0005359. https://doi.org/10.1371/journal.pntd.0005359

 

Regenerative Medicine. S.G.Davies, P.D.Kennewell, A.J.Russell, L.Silpa, R.Westwood, G.M.Wynne. in General Perspective – The Future of Drug Discovery, Comprehensive Medicinal Chemistry III 2017, Pages 379-435 https://doi.org/10.1016/B978-0-12-409547-2.12296-6

 

Second-​generation compound for the modulation of utrophin in the therapy of DMD, Simon Guiraud, Sarah E Squire, Benjamin Edwards, Huijia Chen, David T.Burns, Nandini Shah, Arran Babbs,Stephen G. Davies, Graham M Wynne, Angela J. Russell et al,  Human Molecular Genetics 2015, 24(15), 4212-4224 https://doi.org/10.1093/hmg/ddv154

 

Drug Discovery Approaches for Rare Neuromuscular Diseases, Graham M. Wynne & Angela J. Russell in Orphan Drugs and Rare Diseases, RSC Drug Discovery Series, 2014, ISBN-13: 978-1849738064 https://doi.org/10.1039/9781782624202-00257

 

Stemistry: the Control of Stem Cells in situ Using Chemistry. Stephen G. Davies, Peter D. Kennewell, Angela J. Russell, Peter T. Seden, Robert Westwood, Graham M. Wynne; Journal of Medicinal Chemistry 2015, 58(7), 2863-2894 https://doi.org/10.1021/jm500838d

 

Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists. Matteo Gianella-Borradoria, Ivy Christou, Carole J. R. Bataille, Rebecca L. Cross, Graham M. Wynne, David R. Greaves, Angela J. Russell; Bioorg. Med. Chem. 2015, 23(1), 241-263 https://doi.org/10.1016/j.bmc.2014.11.002

 

Structure-​activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-​acetyltransferase. Egleton, James E.; Thinnes, Cyrille C.; Seden, Peter T.; Laurieri, Nicola; Lee, Siu Po; Hadavizadeh, Kate S.; Measures, Angelina R.; Jones, Alan M.; Thompson, Sam; Varney, Amy; Wynne, Graham M.; Ryan, Ali; Sim, Edith; Russell, Angela J; et al Bioorg. Med. Chem. 2014, 22(11), 3030-54 https://doi.org/10.1016/j.bmc.2014.03.015

 

Discovery and SAR of 2-arylbenzotriazoles and 2-arylindazoles as potential treatments for Duchenne muscular dystrophy. De Moor O, Dorgan C. R, Johnson P. D, Lambert A. G, Lecci C, Maillol C, Nugent G, Poignant S. D, Price P. D, Pye R. J, Storer R, Tinsley J. M, Vickers R, Well R, Wilkes F. J, Wilson F. X, Wren S. P, Wynne G. M. Bioorg Med Chem Lett. 2011, 21(16), 4828-31 https://doi.org/10.1016/j.bmcl.2011.06.047

 

Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy. Chancellor D. R, Davies K. E, De Moor O, Dorgan C. R, Johnson P. D, Lambert A. G, Lawrence D, Lecci C, Maillol C, Middleton P. J, Nugent G, Poignant S. D, Potter A. C, Price P. D, Pye R. J, Storer R, Tinsley J. M, van Well R, Vickers R, Vile J, Wilkes F. J, Wilson F. X, Wren S. P, Wynne G. M. J Med Chem. 2011, 54(9), 3241-50 https://doi.org/10.1021/jm200135z

 

OSI-930: A novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models.      Garton, Andrew J.; Crew, Andrew P. A.; Franklin, Maryland; Cooke, Andrew R.; Wynne, Graham M.; Castaldo, Linda; Kahler, Jennifer; Winski, Shannon L.; Franks, April; Brown, Eric N.; Bittner, Mark A.; Keily, John F.; Briner, Paul; Hidden, Chris; Srebernak, Mary C.; Pirrit, Carrie; O'Connor, Matthew; Chan, Anna; Vulevic, Bojana; Henninger, Dwight; Hart, Karen; Sennello, Regina; Li, An-Hu; Zhang, Tao; Richardson, Frank; Emerson, David L.; Castelhano, Arlindo L.; Arnold, Lee D.; Gibson, Neil W.    OSI Pharmaceuticals, Inc.,  Melville,  NY,  USA.    Cancer Research  2006,  66(2),  1015-1024 https://doi.org/10.1158/0008-5472.can-05-2873

 

Evaluation of a new linker system cleaved using samarium(II) iodide. Application in the solid phase synthesis of carbonyl compounds. McKerlie, Fiona; Rudkin, Iain M.; Wynne, Graham; Procter, David J. Department of Chemistry,  University of Glasgow,  Glasgow,  UK. Organic & Biomolecular Chemistry  2005,  3(15),  2805-2816 https://doi.org/10.1039/b506294b

 

Reduction of a-aryloxy carbonyl compounds with samarium(II) iodide. A new traceless linker for the solid phase synthesis of carbonyl compounds. McKerlie, Fiona; Procter, David J.; Wynne, Graham. Department of Chemistry, The Joseph Black Building,  University of Glasgow,  Glasgow,  UK. Chemical Communications 2002,   (6),  584-585 https://doi.org/10.1039/b200365c

 

Synthesis of ent-9a,15a-cyclokaurene from grandiflorenic acid. Zhang, Hongbin; Wynne, Graham; Mander, Lewis N. Research School of Chemistry, Institute of Advanced Studies,  Australian National University,  Canberra,  Australia.  ARKIVOC 2001,  2(8) http://dx.doi.org/10.3998/ark.5550190.0002.806

 

Gibberellin A117 methyl ester, a new antheridiogen from Lygodium circinnatum.      Wynne, Graham; Mander, Lewis N.; Goto, Nobuyuki; Yamane, Hisakazu; Omori, Toshio.    Research School of Chemistry, Institute of Advanced Studies,  Australian National University,  Canberra,  Australia.    Phytochemistry  1998,  49(7),  1837-1840 https://doi.org/10.1016/S0031-9422(98)00415-4

 

An antheridiogen, 13-hydroxy-GA73 methyl ester (GA109), from the fern Lygodium circinatum.      Wynne, Graham M.; Mander, Lewis N.; Oyama, Naomi; Murofushi, Noboru; Yamane, Hisakazu.    Research School of Chemistry,  Australian National University,  Canberra,  Australia.    Phytochemistry  1998,  47(7),  1177-1182 https://doi.org/10.1016/S0031-9422(97)00714-0

 

Biosynthetic origin of the antheridiogen, gibberellin A73 methyl ester, in ferns of the Lygodium genus.      Wynne, Graham M.; Mander, Lewis N.; Goto, Nobuyuki; Yamane, Hisakazu; Omori, Toshio.    Res. Sch. Chem.,  Inst. Advanced Studies, Australian National Univ.,  Canberra,  Australia.    Tetrahedron Letters  1998,  39(22),  3877-3880 https://doi.org/10.1016/S0040-4039(98)00606-6

 

Synthesis of 12-hydroxy-9,15-cyclogibberellins.  Pour, Milan; Wynne, Graham M.; Mander, Lewis N.; Willis, Anthony C. Research School of Chemistry, Institute of Advanced Studies, Australian National University,  Canberra,  Australia. Tetrahedron Letters  1998,  39(14),  1991-1994 https://doi.org/10.1016/S0040-4039(98)00113-0