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Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR).
Ward RA, Anderton MJ, Ashton S, Bethel PA, Box M, Butterworth S, Colclough N, Chorley CG, Chuaqui C, Cross DA, Dakin LA, Debreczeni JÉ, Eberlein C, Finlay MR, Hill GB, Grist M, Klinowska TC, Lane C, Martin S, Orme JP, Smith P, Wang F, Waring MJ. Ward RA, et al. J Med Chem. 2013 Sep 12;56(17):7025-48. doi: 10.1021/jm400822z. Epub 2013 Aug 30. J Med Chem. 2013. PMID: 23930994
AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.
Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W. Cross DA, et al. Among authors: ward ra. Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3. Cancer Discov. 2014. PMID: 24893891 Free PMC article.
Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor.
Finlay MR, Anderton M, Ashton S, Ballard P, Bethel PA, Box MR, Bradbury RH, Brown SJ, Butterworth S, Campbell A, Chorley C, Colclough N, Cross DA, Currie GS, Grist M, Hassall L, Hill GB, James D, James M, Kemmitt P, Klinowska T, Lamont G, Lamont SG, Martin N, McFarland HL, Mellor MJ, Orme JP, Perkins D, Perkins P, Richmond G, Smith P, Ward RA, Waring MJ, Whittaker D, Wells S, Wrigley GL. Finlay MR, et al. Among authors: ward ra. J Med Chem. 2014 Oct 23;57(20):8249-67. doi: 10.1021/jm500973a. Epub 2014 Oct 1. J Med Chem. 2014. PMID: 25271963
Antitumor Activity of Osimertinib, an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in NSCLC Harboring EGFR Exon 20 Insertions.
Floc'h N, Martin MJ, Riess JW, Orme JP, Staniszewska AD, Ménard L, Cuomo ME, O'Neill DJ, Ward RA, Finlay MRV, McKerrecher D, Cheng M, Vang DP, Burich RA, Keck JG, Gandara DR, Mack PC, Cross DAE. Floc'h N, et al. Among authors: ward ra. Mol Cancer Ther. 2018 May;17(5):885-896. doi: 10.1158/1535-7163.MCT-17-0758. Epub 2018 Feb 26. Mol Cancer Ther. 2018. PMID: 29483211 Free PMC article.
Alkynyl Benzoxazines and Dihydroquinazolines as Cysteine Targeting Covalent Warheads and Their Application in Identification of Selective Irreversible Kinase Inhibitors.
McAulay K, Hoyt EA, Thomas M, Schimpl M, Bodnarchuk MS, Lewis HJ, Barratt D, Bhavsar D, Robinson DM, Deery MJ, Ogg DJ, Bernardes GJL, Ward RA, Waring MJ, Kettle JG. McAulay K, et al. Among authors: ward ra. J Am Chem Soc. 2020 Jun 10;142(23):10358-10372. doi: 10.1021/jacs.9b13391. Epub 2020 Jun 2. J Am Chem Soc. 2020. PMID: 32412754
Preclinical Comparison of the Blood-brain barrier Permeability of Osimertinib with Other EGFR TKIs.
Colclough N, Chen K, Johnström P, Strittmatter N, Yan Y, Wrigley GL, Schou M, Goodwin R, Varnäs K, Adua SJ, Zhao M, Nguyen DX, Maglennon G, Barton P, Atkinson J, Zhang L, Janefeldt A, Wilson J, Smith A, Takano A, Arakawa R, Kondrashov M, Malmquist J, Revunov E, Vazquez-Romero A, Moein MM, Windhorst AD, Karp NA, Finlay MRV, Ward RA, Yates JWT, Smith PD, Farde L, Cheng Z, Cross DAE. Colclough N, et al. Among authors: ward ra. Clin Cancer Res. 2021 Jan 1;27(1):189-201. doi: 10.1158/1078-0432.CCR-19-1871. Epub 2020 Oct 7. Clin Cancer Res. 2021. PMID: 33028591
Potent and Selective Inhibitors of the Epidermal Growth Factor Receptor to Overcome C797S-Mediated Resistance.
Finlay MRV, Barton P, Bickerton S, Bista M, Colclough N, Cross DAE, Evans L, Floc'h N, Gregson C, Guérot CM, Hargreaves D, Kang X, Lenz EM, Li X, Liu Y, Lorthioir O, Martin MJ, McKerrecher D, McWhirter C, O'Neill D, Orme JP, Mosallanejad A, Rahi A, Smith PD, Talbot V, Ward RA, Wrigley G, Wylot M, Xue L, Yao T, Ye Y, Zhao X. Finlay MRV, et al. Among authors: ward ra. J Med Chem. 2021 Sep 23;64(18):13704-13718. doi: 10.1021/acs.jmedchem.1c01055. Epub 2021 Sep 7. J Med Chem. 2021. PMID: 34491761
Targeting Cytotoxic Agents through EGFR-Mediated Covalent Binding and Release.
Morese PA, Anthony N, Bodnarchuk M, Jennings C, Martin MP, Noble RA, Phillips N, Thomas HD, Wang LZ, Lister A, Noble MEM, Ward RA, Wedge SR, Stewart HL, Waring MJ. Morese PA, et al. Among authors: ward ra. J Med Chem. 2023 Sep 14;66(17):12324-12341. doi: 10.1021/acs.jmedchem.3c00845. Epub 2023 Aug 30. J Med Chem. 2023. PMID: 37647129 Free PMC article.
297 results