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Your search keyword '"Louise D. Johnson"' showing total 2 results
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2 results on '"Louise D. Johnson"'

1. Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo

Author

Rosemary Huckvale, Alice C. Harnden, Kwai-Ming J. Cheung, Olivier A. Pierrat, Rachel Talbot, Gary M. Box, Alan T. Henley, Alexis K. de Haven Brandon, Albert E. Hallsworth, Michael D. Bright, Hafize Aysin Akpinar, Daniel S. J. Miller, Dalia Tarantino, Sharon Gowan, Angela Hayes, Emma A. Gunnell, Alfie Brennan, Owen A. Davis, Louise D. Johnson, Selby de Klerk, Craig McAndrew, Yann-Vaï Le Bihan, Mirco Meniconi, Rosemary Burke, Vladimir Kirkin, Rob L. M. van Montfort, Florence I. Raynaud, Olivia W. Rossanese, Benjamin R. Bellenie, and Swen Hoelder

Subjects
Gene Expression Regulation, Neoplastic, Mice, Carcinogenesis, Drug Discovery, Proto-Oncogene Proteins c-bcl-6, Animals, Humans, Molecular Medicine
Abstract

The transcriptional repressor BCL6 is an oncogenic driver found to be deregulated in lymphoid malignancies. Herein, we report the optimization of our previously reported benzimidazolone molecular glue-type degrader

Published
2022
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2. Achieving

Author

Benjamin R, Bellenie, Kwai-Ming J, Cheung, Ana, Varela, Olivier A, Pierrat, Gavin W, Collie, Gary M, Box, Michael D, Bright, Sharon, Gowan, Angela, Hayes, Matthew J, Rodrigues, Kartika N, Shetty, Michael, Carter, Owen A, Davis, Alan T, Henley, Paolo, Innocenti, Louise D, Johnson, Manjuan, Liu, Selby, de Klerk, Yann-Vaï, Le Bihan, Matthew G, Lloyd, P Craig, McAndrew, Erald, Shehu, Rachel, Talbot, Hannah L, Woodward, Rosemary, Burke, Vladimir, Kirkin, Rob L M, van Montfort, Florence I, Raynaud, Olivia W, Rossanese, and Swen, Hoelder

Subjects
Male, Mice, Inbred BALB C, Mice, SCID, Xenograft Model Antitumor Assays, Article, Protein Structure, Tertiary, Rats, Rats, Sprague-Dawley, Mice, Drug Delivery Systems, immune system diseases, hemic and lymphatic diseases, Cell Line, Tumor, Drug Discovery, Microsomes, Liver, Proto-Oncogene Proteins c-bcl-6, Animals, Humans, Benzimidazoles, Female
Abstract

Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein we report the discovery of a series of benzimidazolone inhibitors of the protein–protein interaction between BCL6 and its co-repressors. A subset of these inhibitors were found to cause rapid degradation of BCL6, and optimization of pharmacokinetic properties led to the discovery of 5-((5-chloro-2-((3R,5S)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)pyrimidin-4-yl)amino)-3-(3-hydroxy-3-methylbutyl)-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (CCT369260), which reduces BCL6 levels in a lymphoma xenograft mouse model following oral dosing.

Published
2020

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