James T. Lynch
AstraZeneca
7 Papers
James T. Lynch is an academic researcher from AstraZeneca. The author has contributed to research in topics: PI3K/AKT/mTOR pathway & In vivo. The author has an hindex of 6, co-authored 7 publications.
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Papers
Drug mechanism-of-action discovery through the integration of pharmacological and CRISPR screens
Emanuel Gonçalves,Aldo Segura-Cabrera,Clare Pacini,Gabriele Picco,Fiona M. Behan,Patricia Jaaks,Elizabeth A. Coker,Donny van der Meer,Andrew Barthorpe,Howard Lightfoot,Gdsc Screening Team,Andrew R. Leach,James T. Lynch,Ben Sidders,Claire Crafter,Francesco Iorio,Stephen Fawell,Mathew J. Garnett +17 more
TL;DR: Linking drug and gene dependency together with genomic datasets uncovered contexts in which molecular networks when perturbed mediate cancer cell loss-of-fitness, and thereby provide independent and orthogonal evidence of biomarkers for drug development.
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Inhibiting PI3Kβ with AZD8186 Regulates Key Metabolic Pathways in PTEN-Null Tumors.
James T. Lynch,Urszula M. Polanska,Oona Delpuech,Urs Hancox,Antonio García Trinidad,Filippos Michopoulos,Carol Lenaghan,Robert McEwen,James R. Bradford,Radek Polanski,Rebecca Ellston,Alvaro Avivar-Valderas,James Pilling,Anna Staniszewska,Marie Cumberbatch,Susan E. Critchlow,Francisco Cruzalegui,Simon T. Barry +17 more
TL;DR: Novel mechanistic biomarkers of PI3Kβ inhibition in PTEN-null tumors are identified supporting the concept that targeting PI3kβ may exploit a metabolic dependency that contributes to therapeutic benefit in inducing cell stress.
Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen.
James T. Lynch,Robert McEwen,Claire Crafter,Ultan McDermott,Mathew J. Garnett,Simon T. Barry,Barry R. Davies +6 more
TL;DR: It is demonstrated that T-ALL cell lines show differential sensitivity to inhibition at different nodes in the PI3K/AKT/mTOR pathway and inhibiting AKT or mTOR may have a therapeutic benefit in this disease setting.
Combined Inhibition of PI3Kβ and mTOR Inhibits Growth of PTEN-null Tumors.
James T. Lynch,Urszula M. Polanska,Ursula Hancox,Oona Delpuech,Juliana Maynard,Catherine B. Trigwell,Catherine Anne Eberlein,Carol Lenaghan,Radoslaw Polanski,Alvaro Avivar-Valderas,Marie Cumberbatch,Teresa Klinowska,Susan E. Critchlow,Francisco Cruzalegui,Simon T. Barry +14 more
TL;DR: Combining the PI3Kβ inhibitor AZD8186 and vistusertib has potential to be an effective combination treatment for PTEN-null tumors and in vivo biomarker analysis revealed that the monotherapy and combination treatment consistently reduced similar biomarkers, while combination increased nuclear translocation of the transcription factor FOXO3 and reduction in glucose uptake.
Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model.
Claudia De Fusco,Marianne Schimpl,Ulf Börjesson,Tony Cheung,I. Collie,L. Evans,Priyanka Narasimhan,Christopher D. Stubbs,Mercedes Vazquez-Chantada,David J. Wagner,Michael Grondine,Matthew G Sanders,Sharon Tentarelli,Elizabeth Underwood,Argyrides Argyrou,James M. Smith,James T. Lynch,Elisabetta Chiarparin,Graeme R. Robb,S. Bagal,James S. Scott +20 more
TL;DR: In this paper, a fragment-based lead generation campaign identified weak but efficient hits binding in a known allosteric site and elaborated the hits through a merging and growing strategy into an arylquinazolinone series of potent MAT2a inhibitors.
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