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Discovery and In Vivo Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity.

Autor: Smith JM; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Barlaam B; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Beattie D; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Bradshaw L; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Chan HM; Research and Early Development, Oncology R&D, AstraZeneca, Waltham 02451, United States., Chiarparin E; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Collingwood O; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Cooke SL; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Cronin A; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Cumming I; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Dean E; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Debreczeni JÉ; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Del Barco Barrantes I; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Diene C; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Gianni D; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Guerot C; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Guo X; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Guven S; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Hayhow TG; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Hong T; Research and Early Development, Oncology R&D, AstraZeneca, Waltham 02451, United States., Kemmitt PD; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Lamont GM; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Lamont S; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Lynch JT; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., McWilliams L; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Moore S; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Raubo P; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Robb GR; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Robinson J; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Scott JS; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Srinivasan B; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Steward O; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Stubbs CJ; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Syson K; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Tan L; Pharmaron Beijing Company, Ltd., Beijing 100176, P. R. China., Turner O; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Underwood E; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Urosevic J; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Vazquez-Chantada M; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Whittaker AL; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Wilson DM; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom., Winter-Holt JJ; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2024 Aug 22; Vol. 67 (16), pp. 13604-13638. Date of Electronic Publication: 2024 Jul 30.

Development of a Series of Pyrrolopyridone MAT2A Inhibitors.

Autor: Atkinson SJ; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Bagal SK; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Argyrou A; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Askin S; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Cheung T; Oncology R&D, AstraZeneca, R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Chiarparin E; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Coen M; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Collie IT; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Dale IL; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., De Fusco C; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Dillman K; Oncology R&D, AstraZeneca, R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Evans L; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Feron LJ; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Foster AJ; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Grondine M; Oncology R&D, AstraZeneca, R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Kantae V; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Lamont GM; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Lamont S; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Lynch JT; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Nilsson Lill S; Data Sciences & Modelling, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg 431 83, Sweden., Robb GR; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Saeh J; Oncology R&D, AstraZeneca, R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Schimpl M; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Scott JS; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Smith J; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Srinivasan B; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Tentarelli S; Oncology R&D, AstraZeneca, R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States., Vazquez-Chantada M; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Wagner D; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Walsh JJ; Discovery Sciences R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Watson D; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K., Williamson B; Oncology R&D, AstraZeneca, The Discovery Centre, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge CB2 0AA, U.K.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2024 Mar 28; Vol. 67 (6), pp. 4541-4559. Date of Electronic Publication: 2024 Mar 11.

Chemical Biology Approaches Confirm MCT4 as the Therapeutic Target of a Cellular Optimized Hit.

Autor: Kawatkar A; Discovery Sciences, R&D, AstraZeneca, Waltham, Massachusetts02451, United States., Clark RA; Discovery Sciences, R&D, AstraZeneca, CambridgeCB2 0AA, U.K., Hopcroft L; Oncology R&D, AstraZeneca, CambridgeCB2 0AA, U.K., Roaquin DA; Discovery Sciences, R&D, AstraZeneca, Waltham, Massachusetts02451, United States., Tomlinson R; Discovery Sciences, R&D, AstraZeneca, Waltham, Massachusetts02451, United States., Zuhl AM; Discovery Sciences, R&D, AstraZeneca, Waltham, Massachusetts02451, United States., Lamont GM; Oncology R&D, AstraZeneca, CambridgeCB2 0AA, U.K., Kettle JG; Oncology R&D, AstraZeneca, CambridgeCB2 0AA, U.K., Critchlow SE; Oncology R&D, AstraZeneca, CambridgeCB2 0AA, U.K., Castaldi MP; Discovery Sciences, R&D, AstraZeneca, Waltham, Massachusetts02451, United States., Goldberg FW; Oncology R&D, AstraZeneca, CambridgeCB2 0AA, U.K., Zhang AX; Discovery Sciences, R&D, AstraZeneca, Waltham, Massachusetts02451, United States.

Publikováno v: ACS chemical biology [ACS Chem Biol] 2023 Feb 17; Vol. 18 (2), pp. 296-303. Date of Electronic Publication: 2023 Jan 05.

Optimization of hERG and Pharmacokinetic Properties for Basic Dihydro-8 H -purin-8-one Inhibitors of DNA-PK.

Autor: Goldberg FW; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Ting AKT; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Beattie D; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Lamont GM; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Fallan C; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Finlay MRV; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Williamson B; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Schimpl M; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Harmer AR; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Adeyemi OB; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Nordell P; Biopharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden., Cronin AS; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Vazquez-Chantada M; Discovery Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Barratt D; Discovery Sciences, R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Ramos-Montoya A; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Cadogan EB; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Davies BR; Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K.

Publikováno v: ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 Jul 07; Vol. 13 (8), pp. 1295-1301. Date of Electronic Publication: 2022 Jul 07 (Print Publication: 2022).