Zobrazeno 1 - 10
of 45
pro vyhledávání: '"Graeme R. Robb"'
Publikováno v:
Artificial Intelligence in the Life Sciences, Vol 4, Iss , Pp 100079- (2023)
Deep learning proteochemometric (PCM) models have been reported to achieve excellent performances on public benchmarking datasets. Nevertheless, numerous papers have cast doubt on commonly used evaluation metrics, suggesting they do not reflect true
Externí odkaz:
https://doaj.org/article/45e35c6f8d5a4205986ccbadb74fd45e
Autor:
Graeme R. Robb, Michael S. Bodnarchuk, Jason Grant Kettle, Richard A. Ward, Doyle Joseph Cassar
Publikováno v:
RSC Medicinal Chemistry. 12:609-614
In recent years, the emergence of targeted covalent inhibitors which bind to the G12C mutant of KRAS have offered a solution to this previously intractable target. Inhibitors of KRASG12C tend to be structurally complex, displaying features such as at
Autor:
Iain A. Cumming, Sébastien L. Degorce, Anna Aagaard, Erin L. Braybrooke, Nichola L. Davies, Coura R. Diène, Andrew J. Eatherton, Hannah R. Felstead, Sam D. Groombridge, Eva M. Lenz, Yunxia Li, Youfeng Nai, Stuart Pearson, Graeme R. Robb, James S. Scott, Oliver R. Steward, Chengyan Wu, Yafeng Xue, Lanping Zhang, Yanxiu Zhang
Publikováno v:
Bioorganicmedicinal chemistry. 63
In this article, we report the discovery of a series of pyrimidopyridones as inhibitors of IRAK4 kinase. From a previously disclosed 5-azaquinazoline series, we found that switching the pyridine ring for an N-substituted pyridone gave a novel hinge b
Autor:
Rodrigo J. Carbajo, S. Harlfinger, Lyman Feron, Jason Grant Kettle, E.S. Gleave, Hilary J. Lewis, L. Liu, A. Jackson, Doyle Joseph Cassar, Sharanjeet Kaur Bagal, David Robinson, Radoslaw Polanski, L. Zhang, M.R. Howard, Sabina Cosulich, L. Evans, Jason Breed, Graeme R. Robb, A. Chakraborty, Rachel L. Howells, Rebecca Whiteley, Scott G. Lamont, Lyndsey Hanson, J.K. Kingston, Michael Davies, Iain A. Cumming, Sarah Ross, Sue Bickerton, Paul D. Kemmitt, Derek Ogg, Andrew John Eatherton, James M. Smith, S. Li, Bodnarchuk, Frederick W. Goldberg, Christopher R. Phillips, X. Zhao, Jun Yang, Michael Tonge, Shaun M. Fillery
Publikováno v:
Journal of Medicinal Chemistry. 63:4468-4483
Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small mol
Autor:
Jennifer H. Pink, James S. Scott, Nicola Lindsay, Alan Rosen, Andrew Bloecher, Yafeng Xue, Lisa Drew, Sébastien L. Degorce, Graeme R. Robb, Christopher Thomas Halsall, Rana Anjum, Eva M. Lenz, Rodrigo J. Carbajo, Keith Dillman, Michele Mayo
Publikováno v:
Journal of Medicinal Chemistry. 62:9918-9930
In this article, we report the discovery of a series of 5-azaquinazolines as selective IRAK4 inhibitors. From modestly potent quinazoline 4, we introduced a 5-aza substitution to mask the 4-NH hydrogen bond donor (HBD). This allowed us to substitute
Autor:
Elisabetta Chiarparin, Amber Balazs, Martin J. Packer, Jeffrey W. Johannes, Nichola L. Davies, William McCoull, Graeme R. Robb, Piotr Raubo, Yu Dong, Alexander Hird, Rodrigo J. Carbajo, Michelle Lamb
Publikováno v:
Journal of Medicinal Chemistry. 62:9418-9437
The three-dimensional conformations adopted by a free ligand in solution impact bioactivity and physicochemical properties. Solution 1D NMR spectra inherently contain information on ligand conformational flexibility and three-dimensional shape, as we
Autor:
James M. Smith, Rana Anjum, Sébastien L. Degorce, Ina Terstiege, Turner Paul, Stuart E. Pearson, Michael J. Tucker, Alexandra L. Orton, Charlene Fallan, Graeme Scarfe, Anna Aagaard, James S. Scott, Oliver R. Steward, Yafeng Xue, Iain A. Cumming, Tony Johnson, Gail L. Wrigley, Karl-Johan Leuchowius, Stephen D. Wilkinson, Graeme R. Robb, Coura R. Diène, Alan Rosen
Publikováno v:
Bioorganicmedicinal chemistry. 28(23)
In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism
Autor:
Sébastien L, Degorce, Rana, Anjum, Andrew, Bloecher, Rodrigo J, Carbajo, Keith S, Dillman, Lisa, Drew, Christopher T, Halsall, Eva M, Lenz, Nicola A, Lindsay, Michele F, Mayo, Jennifer H, Pink, Graeme R, Robb, Alan, Rosen, James S, Scott, Yafeng, Xue
Publikováno v:
Journal of medicinal chemistry. 62(21)
In this article, we report the discovery of a series of 5-azaquinazolines as selective IRAK4 inhibitors. From modestly potent quinazoline
Autor:
Camila de-Almeida, Keith R. Mulholland, Kang Zhao, Barlaam Bernard Christophe, Gilles Ouvry, Gareth Hughes, Martin Pass, Elaine Cadogan, Zhenhua Wang, Andrew D. Campbell, Nidal Al-Huniti, Natalie Stratton, Sébastien L. Degorce, Joanne Wilson, Myriam Didelot, Philip A. MacFaul, Stephen T. Durant, Richard Ducray, Baochang Zhai, Kurt Gordon Pike, Lorraine A. Hassall, Jane L. Holmes, Thomas M. McGuire, Nichola L. Davies, Allan Dishington, Yingxue Chen, Nicola Colclough, Graeme R. Robb
Publikováno v:
Journal of Medicinal Chemistry. 61:3823-3841
ATM inhibitors, such as 7, have demonstrated the antitumor potential of ATM inhibition when combined with DNA double-strand break-inducing agents in mouse xenograft models. However, the properties of 7 result in a relatively high predicted clinically
Autor:
Keith Dillman, J. Elizabeth Pease, James E. Dowling, Nichola L. Davies, Rana Anjum, Robert D. M. Davies, Janet D. Culshaw, David R. Perkins, Dedong Wu, Julian A. Hudson, Sébastien L. Degorce, Jennifer H. Pink, Nicola Lindsay, Christopher Thomas Halsall, James S. Scott, Scott G. Lamont, Minhui Shen, Andrew D. Ferguson, Alan Rosen, Lisa Drew, Stacey Marden, Claire McWhirter, Sam D. Groombridge, Michele Mayo, Graeme R. Robb
Publikováno v:
Journal of Medicinal Chemistry. 60:10071-10091
Herein we report the optimization of a series of pyrrolopyrimidine inhibitors of interleukin-1 receptor associated kinase 4 (IRAK4) using X-ray crystal structures and structure based design to identify and optimize our scaffold. Compound 28 demonstra