T
T.G. Davies
Researcher at Astex
Publications - 23
Citations - 1239
T.G. Davies is an academic researcher from Astex. The author has contributed to research in topics: Protein kinase B & Fragment-based lead discovery. The author has an hindex of 15, co-authored 23 publications receiving 1050 citations. Previous affiliations of T.G. Davies include Institute of Cancer Research.
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Journal ArticleDOI
Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery
T.G. Davies,William E. Wixted,Joseph E. Coyle,Charlotte Mary Griffiths-Jones,Keisha Hearn,Rachel McMenamin,David Norton,Sharna J. Rich,Caroline Richardson,Gordon Saxty,Henriëtte M. G. Willems,Alison Jo-Anne Woolford,Joshua E. Cottom,Jen-Pyng Kou,John Yonchuk,Heidi G. Feldser,Yolanda Sanchez,Joseph P. Foley,Brian Bolognese,Gregory A. Logan,Patricia L. Podolin,Hongxing Yan,James F. Callahan,Tom D. Heightman,Jeffrey K. Kerns +24 more
TL;DR: This work resulted in a promising lead compound which exhibits tight and selective binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in vivo models, thereby providing a high quality chemical probe to explore the therapeutic potential of disrupting theKEAP1-NRF2 interaction.
Journal ArticleDOI
Structure of the Btb Domain of Keap1 and its Interaction with the Triterpenoid Antagonist Cddo.
Anne Cleasby,Jeff Yon,Philip J. Day,Caroline Richardson,Ian J. Tickle,Pamela A. Williams,James F. Callahan,Robin Carr,Nestor O. Concha,Jeffrey K. Kerns,Hongwei Qi,Thomas D. Sweitzer,Paris Ward,T.G. Davies +13 more
TL;DR: The first structure of the BTB domain of Keap1 is reported, which is thought to contain the key cysteine residue responsible for interaction with electrophiles, as well as structures of the covalent complex with the antagonist CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant.
Journal ArticleDOI
Identification of Inhibitors of Protein Kinase B Using Fragment-Based Lead Discovery
Gordon Saxty,Steven John Woodhead,Valerio Berdini,T.G. Davies,Marcel L. Verdonk,Paul Graham Wyatt,Robert George Boyle,David Barford,Robert Downham,Michelle D. Garrett,Robin Arthur Ellis Carr +10 more
TL;DR: This work describes the rapid elaboration of highly potent and ligand efficient analogues using a fragment growing approach to identify a novel, low molecular weight inhibitor of protein kinase B (PKB).
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Identification of 4-(4-aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as selective inhibitors of protein kinase B through fragment elaboration.
John J. Caldwell,T.G. Davies,A. Donald,T. McHardy,Martin G. Rowlands,G.W. Aherne,L.K. Hunter,K. Taylor,Ruth Ruddle,Florence I. Raynaud,Marcel L. Verdonk,Paul Workman,Garrett,Ian Collins +13 more
TL;DR: Fragment-based screening identified 7-azaindole as a protein kinase B inhibitor scaffold and the most PKB-selective inhibitor (30-fold) showed significantly different bound conformations between PKA and PKA-PKB chimera.
Journal ArticleDOI
AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity.
Timothy A. Yap,Michael I. Walton,Kyla Grimshaw,Robert te Poele,Paul D. Eve,Melanie Valenti,Alexis De Haven Brandon,Vanessa Martins,Anna Zetterlund,Simon P. Heaton,Kathrin Heinzmann,Paul S. Jones,Ruth Feltell,Matthias Reule,Steven John Woodhead,T.G. Davies,John Lyons,Florence I. Raynaud,Suzanne A. Eccles,Paul Workman,Neil T. Thompson,Michelle D. Garrett +21 more
TL;DR: Gene expression studies showed that AT13148 has a predominant effect on apoptosis genes, whereas the selective AKT inhibitor CCT128930 modulates cell-cycle genes, which shows a distinct mechanism of action from other AKT inhibitors.