Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRASG12C

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

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::0c0d1227f159830cde7d87c48972047a
https://doi.org/10.1021/acs.jmedchem.9b01720

Iridium-Catalyzed α-Selective Arylation of Styrenes by Dual C−H Functionalization

Autor: John F. Bower, Phillippa Cooper, Lyman Feron, Giacomo E. M. Crisenza

Publikováno v: Angewandte Chemie (International Ed. in English)
Cooper, P, Crisenza, G, Feron, L & Bower, J 2018, ' Iridium-Catalyzed α-Selective Arylation of Styrenes by Dual C-H Functionalization ', Angewandte Chemie-International Edition, vol. 57, pp. 14198-14202 . https://doi.org/10.1002/anie.201808299

An IrI‐system modified with a ferrocene derived bisphosphine ligand promotes α‐selective arylation of styrenes by dual C−H functionalization. These studies offer a regioisomeric alternative to the Pd‐catalyzed Fujiwara–Moritani reaction.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1eb74b66248981c2f8cb5f7b861a6b95
https://doi.org/10.1002/ange.201808299

Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC)

Autor: Jia Tang, Richard A. Ward, Paul A. Bethel, Scott G. Lamont, Julian A. Hudson, Philip Hopcroft, Clifford David Jones, Steve Swallow, Richard J. Lewis, Tomkinson Gary Peter, Baochang Zhai, Nicola Lindsay, Jason Breed, Emma J. Davies, Yongchao Li, Vikki Flemington, Michael Tonge, Paul Farrington, Ryan Greenwood, Mark A. Graham, Linda Sandin, Thomas M. McGuire, James F. McCabe, Mark J. Anderton, Michael R. James, Andrew Hornby Dobson, Philip B. Rawlins, Lyndsey Hanson, Iain Simpson, Karen Roberts, Gary Fairley, Rachel L. Howells, Christopher R. Jones, Calum Cook, Francis D. Gibbons, Zhiqiang Dong, Lyman Feron, Zhenhua Wang

Publikováno v: Journal of medicinal chemistry. 62(24)

The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68575e1f1cd6f592b8ead892c32d4cc6
https://pubmed.ncbi.nlm.nih.gov/31710489

Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist

Autor: Craig S. Donald, Galith Karoutchi, Syeed Hussain, Peter Ballard, Gordon S. Currie, Barry R. Hayter, Hazel M. Weir, H. Gingell, Richard A. Norman, Steven C. Glossop, David Buttar, Lyman Feron, Zena Wilson, Stuart E. Pearson, Camila de Almeida, Christopher D. Davies, Rowena Callis, Philip A. MacFaul, Thomas A. Moss, Chris De Savi, Alfred A. Rabow, David M. Andrews, Graeme Walker, Michael Tonge, Scott G. Lamont, Jon Curwen, Robert Hugh Bradbury

Publikováno v: Journal of Medicinal Chemistry. 58:8128-8140

The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified the 1-aryl-2,3,4,9-tetrahyd

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::a9d21c50ca9de0e32e23964631039a67
https://doi.org/10.1021/acs.jmedchem.5b00984

Regioselective ortho alkylation of nitro indole, carbazole, benzothiophene and benzofuran

Autor: Lamont, Scott G., Donald, Craig S., Lyman Feron, J., Groombridge, Sam D.

Publikováno v: In Tetrahedron Letters 30 December 2015 56(52):7165-7167