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.

Structure-Guided Design of a Domain-Selective Bromodomain and Extra Terminal N-Terminal Bromodomain Chemical Probe.

Autor: Bradley E; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K.; Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, U.K., Fusani L; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K.; Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, U.K., Chung CW; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Craggs PD; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Demont EH; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Humphreys PG; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Mitchell DJ; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Phillipou A; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Rioja I; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Shah RR; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Wellaway CR; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Prinjha RK; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Palmer DS; Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, U.K., Kerr WJ; Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, U.K., Reid M; Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, U.K., Wall ID; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K., Cookson R; GSK, Medicines Research Centre, Stevenage SG1 2NY, Hertfordshire, U.K.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2023 Dec 14; Vol. 66 (23), pp. 15728-15749. Date of Electronic Publication: 2023 Nov 15.

Enhancing Ligand and Protein Sampling Using Sequential Monte Carlo.

Autor: Suruzhon M; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K., Bodnarchuk MS; Computational Chemistry, R&D Oncology, AstraZeneca, Cambridge CB4 0WG, U.K., Ciancetta A; Sygnature Discovery, Bio City, Pennyfoot Street, Nottingham NG1 1GR, U.K.; Department of Chemical, Pharmaceutical and Agricultural Sciences─DOCPAS, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy., Wall ID; GSK Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, U.K., Essex JW; School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K.

Publikováno v: Journal of chemical theory and computation [J Chem Theory Comput] 2022 Jun 14; Vol. 18 (6), pp. 3894-3910. Date of Electronic Publication: 2022 May 19.

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.

Discovery of a Highly Selective BET BD2 Inhibitor from a DNA-Encoded Library Technology Screening Hit.

Autor: Rianjongdee F, Atkinson SJ, Chung CW, Grandi P; IVIVT Cellzome, Platform Technology and Science, GlaxoSmithKline, Meyerhofstr. 1, Heidelberg 69117, Germany., Gray JRJ, Kaushansky LJ; Encoded Library Technologies, R&D Medicinal Science and Technology, GSK, 200 Cambridge Park Drive, Cambridge 02140, Massachusetts, United States., Medeiros P; Encoded Library Technologies, R&D Medicinal Science and Technology, GSK, 200 Cambridge Park Drive, Cambridge 02140, Massachusetts, United States., Messenger C, Phillipou A, Preston A, Prinjha RK, Rioja I, Satz AL; WuXi AppTec (Shanghai) Co., Ltd., Shanghai 200131, China., Taylor S, Wall ID, Watson RJ, Yao G; Encoded Library Technologies, R&D Medicinal Science and Technology, GSK, 200 Cambridge Park Drive, Cambridge 02140, Massachusetts, United States., Demont EH

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2021 Aug 12; Vol. 64 (15), pp. 10806-10833. Date of Electronic Publication: 2021 Jul 12.