R
Robert J. Sheppard
Researcher at GlaxoSmithKline
Publications - 28
Citations - 2040
Robert J. Sheppard is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Bromodomain & Demethylase. The author has an hindex of 15, co-authored 28 publications receiving 1730 citations. Previous affiliations of Robert J. Sheppard include Virginia Tech & AstraZeneca.
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Journal ArticleDOI
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response
Laurens Kruidenier,Chun-wa Chung,Zhongjun Cheng,John Liddle,K.H. Che,K.H. Che,Gerard Joberty,Marcus Bantscheff,C. Bountra,Angela Bridges,Hawa Diallo,Dirk Eberhard,Sue Hutchinson,Emma J. Jones,Roy Katso,Melanie Leveridge,Palwinder K. Mander,J. Mosley,Cesar Ramirez-Molina,Paul Rowland,Christopher J. Schofield,Robert J. Sheppard,Julia Smith,Catherine Swales,Robert Tanner,Pamela Thomas,Anthony Tumber,Gerard Drewes,Udo Oppermann,Udo Oppermann,Dinshaw J. Patel,Kevin Lee,Kevin Lee,David Matthew Wilson +33 more
TL;DR: It is demonstrated that the first small-molecule catalytic site inhibitor that is selective for the H3K27me3-specific JMJ subfamily binds in a novel manner and reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX.
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Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation
Huw D. Lewis,John Liddle,Jim E Coote,Stephen John Atkinson,Michael David Barker,Benjamin D. Bax,Kevin L. Bicker,Ryan P. Bingham,Matthew Campbell,Yu Hua Chen,Chun-wa Chung,Peter D. Craggs,Robert P. Davis,Dirk Eberhard,Gerard Joberty,Kenneth E Lind,Kelly Locke,Claire Maller,Kimberly Martinod,Chris Patten,Oxana Polyakova,Cecil E Rise,Martin Rüdiger,Robert J. Sheppard,Daniel J. Slade,Pamela Thomas,Jim Thorpe,Gang Yao,Gerard Drewes,Denisa D. Wagner,Paul R. Thompson,Rab K. Prinjha,David Matthew Wilson +32 more
TL;DR: Novel, selective PAD4 inhibitors binding to a calcium-deficient form of the PAD3 enzyme have been validated, for the first time, in both histone citrullination and neutrophil extracellular trap formation, validating the critical enzymatic role of human and mouse PAD 4.
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Nanomolar Inhibitors of Staphylococcus aureus Methionyl tRNA Synthetase with Potent Antibacterial Activity against Gram-Positive Pathogens
Richard L. Jarvest,John M. Berge,Valerie Berry,Helen F. Boyd,Murray J. B. Brown,John S. Elder,Andrew Keith Forrest,Andrew P. Fosberry,Daniel R. Gentry,Martin Hibbs,Deborah Dee Jaworski,Peter J. O'Hanlon,Andrew J. Pope,Stephen Rittenhouse,Robert J. Sheppard,Courtney Slater-Radosti,Angela Worby +16 more
TL;DR: Optimized compounds show excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics, and demonstrated in vivo efficacy in an S. aureus rat abscess infection model.
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Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors.
Paul Bamborough,Chun-wa Chung,Rebecca C. Furze,Paola Grandi,Anne-Marie Michon,Robert J. Sheppard,Heather A. Barnett,Hawa Diallo,David P. Dixon,Clement Douault,Emma J. Jones,Bhumika Karamshi,Darren Jason Mitchell,Rab K. Prinjha,Christina Rau,Robert J. Watson,Thilo Werner,Emmanuel Hubert Demont +17 more
TL;DR: This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.
Journal ArticleDOI
1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain
Emmanuel Hubert Demont,Paul Bamborough,Chun-wa Chung,Peter D. Craggs,David J. Fallon,Laurie J. Gordon,Paola Grandi,Clare I. Hobbs,Jameed Hussain,Emma J. Jones,Armelle Le Gall,Anne-Marie Michon,Darren Jason Mitchell,Rab K. Prinjha,Andrew D. Roberts,Robert J. Sheppard,Robert J. Watson +16 more
TL;DR: The discovery, binding mode, and structure-activity relationship (SAR) of the first potent, selective series of inhibitors of the BRPF1 bromodomain are reported.