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Antonia J. Lewis
Researcher at GlaxoSmithKline
Publications - 9
Citations - 744
Antonia J. Lewis is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Bromodomain & Gene. The author has an hindex of 5, co-authored 9 publications receiving 600 citations.
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Journal ArticleDOI
Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains
Olivier Mirguet,Romain Luc Marie Gosmini,Jérôme Toum,Catherine A. Clément,Mélanie Barnathan,Jean-Marie Brusq,Jacqueline Elizabeth Mordaunt,Grimes Richard Martin,Miriam Crowe,Olivier Pineau,Myriam Ajakane,Alain Claude-Marie Daugan,Phillip Jeffrey,Leanne Cutler,Andrea C. Haynes,Nicholas Smithers,Chun-wa Chung,Paul Bamborough,Iain Uings,Antonia J. Lewis,Jason Witherington,Nigel J. Parr,Rab K. Prinjha,Edwige Nicodeme +23 more
TL;DR: This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.
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Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides.
Paul Bamborough,Hawa Diallo,Jonathan D. Goodacre,Laurie J. Gordon,Antonia J. Lewis,Jonathan Thomas Seal,David Matthew Wilson,Woodrow Michael David,Chun-wa Chung +8 more
TL;DR: A phenyl dimethyl isoxazole chemotype resulting from a focused fragment screen has been rapidly optimized through structure-based design, leading to a sulfonamide series showing anti-inflammatory activity in cellular assays.
Journal ArticleDOI
The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor
Romain Luc Marie Gosmini,Van Loc Nguyen,Jérôme Toum,Christophe Simon,Jean-Marie Brusq,Gael Krysa,Olivier Mirguet,Alizon M. Riou-Eymard,Eric Boursier,Lionel Trottet,Paul Bamborough,Hugh Clark,Chun-wa Chung,Leanne Cutler,Emmanuel Hubert Demont,Rejbinder Kaur,Antonia J. Lewis,Mark B. Schilling,Peter Ernest Soden,Simon Taylor,Ann Louise Walker,Matthew D. Walker,Rab K. Prinjha,Edwige Nicodeme +23 more
TL;DR: This work describes the identification of a novel tetrahydroquinoline series through up-regulation of apolipoprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma, and reveals the interactions explaining the structure-activity relationships of binding.
Journal ArticleDOI
Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs.
Robert P. Law,João Osvaldo Rodrigues Nunes,Chun-wa Chung,Marcus Bantscheff,Karol Buda,Han Dai,John P. Evans,Adam Flinders,Diana Klimaszewska,Antonia J. Lewis,Marcel Muelbaier,Paul Scott-Stevens,Peter Stacey,Christopher J. Tame,Gillian F. Watt,Nico Zinn,Markus A. Queisser,John D. Harling,Andrew B. Benowitz +18 more
TL;DR: In this article, a potent, selective, FAK-degrading Proteolysis Targeting Chimera (PROTAC) based on a binder for the VHL E3 ligase and the known FAK inhibitor VS-4718 was presented.
Journal ArticleDOI
Naphthyridines as Novel Bet Family Bromodomain Inhibitors.
Olivier Mirguet,Yann Lamotte,Chun-wa Chung,Paul Bamborough,Delphine Delannée,Anne Marie Jeanne Bouillot,Françoise Gellibert,Gael Krysa,Antonia J. Lewis,Jason Witherington,Pascal Huet,Yann Dudit,Lionel Trottet,Edwige Nicodeme +13 more
TL;DR: 1,5‐naphthyridine derivatives are reported as potent inhibitors of the BET bromodomain family with good cell activity and oral pharmacokinetic parameters and the best compounds were progressed in a mouse model of inflammation and exhibited dose‐dependent anti‐inflammatory pharmacology.