M
Michael Tonge
Researcher at AstraZeneca
Publications - 14
Citations - 686
Michael Tonge is an academic researcher from AstraZeneca. The author has contributed to research in topics: Estrogen receptor & Allosteric regulation. The author has an hindex of 10, co-authored 13 publications receiving 495 citations.
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Journal ArticleDOI
Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRASG12C.
Jason Grant Kettle,Sharan K. Bagal,Susan J. Bickerton,Michael S. Bodnarchuk,Scott Boyd,Jason Breed,Rodrigo J. Carbajo,Doyle Joseph Cassar,Atanu Chakraborty,Sabina Cosulich,Iain Cumming,Michael Davies,Nichola L. Davies,Andrew John Eatherton,L. Evans,Lyman Feron,Shaun M. Fillery,Emma S Gleave,Frederick W. Goldberg,Lyndsey Hanson,Stephanie Harlfinger,M.R. Howard,Rachel L. Howells,Anne U. Jackson,Paul D. Kemmitt,Gillian M. Lamont,Scott G. Lamont,Hilary J. Lewis,Libin Liu,Michael J. Niedbala,Christopher R. Phillips,R. Polanski,Piotr Raubo,Graeme R. Robb,David A. Robinson,Sarah Ross,Matthew Sanders,Michael Tonge,Rebecca Whiteley,Stephen D. Wilkinson,Junsheng Yang,Wenman Zhang +41 more
TL;DR: A structure-based drug design approach that led to the identification of 21, AZD4625, a clinical development candidate for the treatment of KRASG12C positive tumors, with an anticipated low clearance and high oral bioavailability profile in humans.
Journal ArticleDOI
AZD0364 Is a Potent and Selective ERK1/2 Inhibitor That Enhances Antitumor Activity in KRAS-Mutant Tumor Models when Combined with the MEK Inhibitor, Selumetinib.
Vikki Flemington,Emma J. Davies,David Robinson,Linda Sandin,Oona Delpuech,Pei Zhang,Lyndsey Hanson,Paul Farrington,Sigourney Bell,Katarzyna Falenta,Francis D. Gibbons,Nicola Lindsay,Aaron Smith,Joanne Wilson,Karen Roberts,Michael Tonge,Philip Hopcroft,Sophie E. Willis,Martine P. Roudier,Claire Rooney,Elizabeth A. Coker,Patricia Jaaks,Mathew J. Garnett,Stephen Fawell,Clifford David Jones,Richard A. Ward,Iain Simpson,Sabina Cosulich,J. Elizabeth Pease,Paul D. Smith +29 more
TL;DR: The discovery and characterization of AZD0364, a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and kinase selectivity, and selumetinib combination, which enhances efficacy in KRAS-mutant preclinical models that are moderately sensitive or resistant to MEK 1/2 inhibition.
Proceedings ArticleDOI
Abstract 3650: Discovery of the clinical candidate AZD9496: a potent and orally bioavailable selective estrogen receptor downregulator and antagonist
Chris De Savi,Robert Hugh Bradbury,Alfred A. Rabow,Richard A. Norman,David Buttar,Gordon S. Currie,Hazel M. Weir,Craig S. Donald,David M. Andrews,Phil MacFaul,Peter Ballard,Jon Curwen,Zena Wilson,Graham Richmond,Celina M. D'Cruz,Steve Powell,Graeme Walker,Michael Hulse,Michael Tonge +18 more
TL;DR: Data will be shared for the first time on the medicinal chemistry efforts that led to AZD9496, the good oral pharmacokinetic properties of the compound which led to significant tumor efficacy in both endocrine sensitive model and resistant models.
Proceedings ArticleDOI
Abstract DDT01-03: Discovery and pre-clinical pharmacology of AZD9496: An oral, selective estrogen receptor down-regulator (SERD)
Hazel M. Weir,Mandy Lawson,Rowena Callis,Michael Hulse,Michael Tonge,Gareth M. Davies,Graeme Walker,Rachel Rowlinson,Jon Curwen,Zena Wilson,Steve Powell,Robert Hugh Bradbury,Alfred A. Rabow,Craig S. Donald,David Buttar,Richard A. Norman,Camila de Almeida,Peter Ballard,Gordon S. Currie,David M. Andrews,Graham Richmond,Anne Marie Mazzola,Ermira Pazolli,Brendon Ladd,Celina M. D'Cruz,Chris De Savi +25 more
TL;DR: The discovery and pre-clinical pharmacology of AZD9496, a small molecule that can antagonise ERα and induce receptor degradation in breast cancer cell lines at picomolar concentrations, and the drug is under evaluation in a Phase 1 clinical trial.