Structure- and Property-Based Optimization of Efficient Pan-Bromodomain and Extra Terminal Inhibitors to Identify Oral and Intravenous Candidate I-BET787.

Autor: Hirst DJ; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Bamborough P; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Al-Mahdi N; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Angell DC; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Barnett HA; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Baxter A; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Bit RA; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Brown JA; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Chung CW; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Craggs PD; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Davis RP; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Demont EH; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Ferrie A; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Gordon LJ; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Harada I; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Ho TCT; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Holyer ID; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Hooper-Greenhill E; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Jones KL; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Lindon MJ; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Lovatt C; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Lugo D; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Maller C; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., McGonagle G; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Messenger C; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Mitchell DJ; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Pascoe DD; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Patel VK; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Patten C; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Poole DL; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Shah RR; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Rioja I; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Stafford KAJ; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Tape D; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Taylor S; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Theodoulou NH; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Tomlinson L; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Wall ID; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Wellaway CR; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., White G; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Prinjha RK; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Humphreys PG; GSK Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2024 Jun 27; Vol. 67 (12), pp. 10464-10489. Date of Electronic Publication: 2024 Jun 12.

Enhancing torsional sampling using fully adaptive simulated tempering.

Autor: Suruzhon M; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom., Abdel-Maksoud K; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom., Bodnarchuk MS; Computational Chemistry, R&D Oncology, AstraZeneca, Cambridge CB4 0WG, United Kingdom., Ciancetta A; Sygnature Discovery Limited, Nottingham NG1 1GR, United Kingdom., Wall ID; GSK Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom., Essex JW; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.

Publikováno v: The Journal of chemical physics [J Chem Phys] 2024 Apr 21; Vol. 160 (15).

Identification and Optimization of a Ligand-Efficient Benzoazepinone Bromodomain and Extra Terminal (BET) Family Acetyl-Lysine Mimetic into the Oral Candidate Quality Molecule I-BET432.

Autor: Humphreys PG; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Anderson NA; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Bamborough P; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Baxter A; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Chung CW; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Cookson R; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Craggs PD; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Dalton T; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Fournier JCL; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Gordon LJ; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Gray HF; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Gray MW; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Gregory R; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Hirst DJ; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Jamieson C; WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, U.K., Jones KL; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Kessedjian H; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Lugo D; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., McGonagle G; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Patel VK; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Patten C; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Poole DL; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Prinjha RK; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Ramirez-Molina C; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Rioja I; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Seal G; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Stafford KAJ; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Shah RR; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Tape D; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Theodoulou NH; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Tomlinson L; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Ukuser S; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Wall ID; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., Wellaway N; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K., White G; GSK, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, U.K.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2022 Nov 24; Vol. 65 (22), pp. 15174-15207. Date of Electronic Publication: 2022 Nov 15.

Ensemble Simulations and Experimental Free Energy Distributions: Evaluation and Characterization of Isoxazole Amides as SMYD3 Inhibitors.

Autor: Wan S; Centre for Computational Science, Department of Chemistry, University College London, London WC1H 0AJ, U.K., Bhati AP; Centre for Computational Science, Department of Chemistry, University College London, London WC1H 0AJ, U.K., Wright DW; Centre for Computational Science, Department of Chemistry, University College London, London WC1H 0AJ, U.K., Wall ID; GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K., Graves AP; GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., Green D; GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K., Coveney PV; Centre for Computational Science, Department of Chemistry, University College London, London WC1H 0AJ, U.K.; Advanced Research Computing Centre, University College London, London WC1H 0AJ U.K.; Institute for Informatics, Faculty of Science, University of Amsterdam, 1098XH Amsterdam, The Netherlands.

Publikováno v: Journal of chemical information and modeling [J Chem Inf Model] 2022 May 23; Vol. 62 (10), pp. 2561-2570. Date of Electronic Publication: 2022 May 04.

Fragment-based Scaffold Hopping: Identification of Potent, Selective, and Highly Soluble Bromo and Extra Terminal Domain (BET) Second Bromodomain (BD2) Inhibitors.

Autor: Seal JT, Atkinson SJ, Bamborough P, Bassil A, Chung CW, Foley J; Cancer Epigenetics Research Unit, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., Gordon L, Grandi P; IVIVT Cellzome, Platform Technology and Science, GlaxoSmithKline, Meyerhofstr. 1, 69117 Heidelberg, Germany., Gray JRJ, Harrison LA, Kruger RG; Cancer Epigenetics Research Unit, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., Matteo JJ; Cancer Epigenetics Research Unit, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., McCabe MT; Cancer Epigenetics Research Unit, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., Messenger C, Mitchell D, Phillipou A, Preston A, Prinjha RK, Rianjongdee F, Rioja I, Taylor S, Wall ID, Watson RJ, Woolven JM, Wyce A; Cancer Epigenetics Research Unit, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., Zhang XP; Cancer Epigenetics Research Unit, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States., Demont EH

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2021 Aug 12; Vol. 64 (15), pp. 10772-10805. Date of Electronic Publication: 2021 Jul 13.