Bromodomain inhibitor i-BET858 triggers a unique transcriptional response coupled to enhanced DNA damage, cell cycle arrest and apoptosis in high-grade ovarian carcinoma cells

Autor: Marcos Quintela, David W. James, Agne Pociute, Lydia Powell, Kadie Edwards, Zoe Coombes, Jetzabel Garcia, Neil Garton, Nagindra Das, Kerryn Lutchman-Singh, Lavinia Margarit, Amy L. Beynon, Inmaculada Rioja, Rab K. Prinjha, Nicola R. Harker, Deyarina Gonzalez, R. Steven Conlan, Lewis W. Francis

Publikováno v: Clinical Epigenetics, Vol 15, Iss 1, Pp 1-17 (2023)

Abstract Background Ovarian cancer has a specific unmet clinical need, with a persistently poor 5-year survival rate observed in women with advanced stage disease warranting continued efforts to develop new treatment options. The amplification of BRD

Externí odkaz: https://doaj.org/article/7e33d7221ca149fd99b604385784b7c0

Bromodomain factor 5 is an essential regulator of transcription in Leishmania

Autor: Nathaniel G. Jones, Vincent Geoghegan, Gareth Moore, Juliana B. T. Carnielli, Katherine Newling, Félix Calderón, Raquel Gabarró, Julio Martín, Rab K. Prinjha, Inmaculada Rioja, Anthony J. Wilkinson, Jeremy C. Mottram

Publikováno v: Nature Communications, Vol 13, Iss 1, Pp 1-18 (2022)

Leishmania use large (5–10 kb) transcriptional start regions, where the chromatin is highly enriched for acetylated histones, to drive the expression of polycistronic gene arrays. Here the authors show bromodomain-containing protein BDF5 is enriche

Externí odkaz: https://doaj.org/article/1db1b17d7f85497d9117d4a2f66ff272

Combined noncanonical NF-κB agonism and targeted BET bromodomain inhibition reverse HIV latency ex vivo

Autor: Shane D. Falcinelli, Jackson J. Peterson, Anne-Marie W. Turner, David Irlbeck, Jenna Read, Samuel L.M. Raines, Katherine S. James, Cameron Sutton, Anthony Sanchez, Ann Emery, Gavin Sampey, Robert Ferris, Brigitte Allard, Simon Ghofrani, Jennifer L. Kirchherr, Caroline Baker, JoAnn D. Kuruc, Cynthia L. Gay, Lindsey I. James, Guoxin Wu, Paul Zuck, Inmaculada Rioja, Rebecca C. Furze, Rab K. Prinjha, Bonnie J. Howell, Ronald Swanstrom, Edward P. Browne, Brian D. Strahl, Richard M. Dunham, Nancie M. Archin, David M. Margolis

Publikováno v: The Journal of Clinical Investigation, Vol 132, Iss 8 (2022)

Latency reversal strategies for HIV cure using inhibitor of apoptosis protein (IAP) antagonists (IAPi) induce unprecedented levels of latent reservoir expression without immunotoxicity during suppressive antiretroviral therapy (ART). However, full ta

Externí odkaz: https://doaj.org/article/4373bee6f4264a5fa37799577488e1df

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: Philip G. Humphreys, Niall A. Anderson, Paul Bamborough, Andrew Baxter, Chun-wa Chung, Rosa Cookson, Peter D. Craggs, Toryn Dalton, Julie C. L. Fournier, Laurie J. Gordon, Heather F. Gray, Matthew W. Gray, Richard Gregory, David J. Hirst, Craig Jamieson, Katherine L. Jones, Hripsimee Kessedjian, David Lugo, Grant McGonagle, Vipulkumar K. Patel, Christopher Patten, Darren L. Poole, Rab K. Prinjha, Cesar Ramirez-Molina, Inmaculada Rioja, Gail Seal, Kayleigh A. J. Stafford, Rishi R. Shah, Daniel Tape, Natalie H. Theodoulou, Laura Tomlinson, Sabri Ukuser, Ian D. Wall, Natalie Wellaway, Gemma White

Publikováno v: Journal of Medicinal Chemistry. 65:15174-15207

The bromodomain and extra terminal (BET) family of proteins are an integral part of human epigenome regulation, the dysregulation of which is implicated in multiple oncology and inflammatory diseases. Disrupting the BET family bromodomain acetyl-lysi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::247c403b556d0cdc2a89bb75345904c1
https://doi.org/10.1021/acs.jmedchem.2c01102

Carboxylesterase-1 Assisted Targeting of HDAC Inhibitors to Mononuclear Myeloid Cells in Inflammatory Bowel Disease

Autor: Patricia van Hamersveld, Laura Tomlinson, Ishtu Hageman, Ahmed M. I. Elfiky, Sigrid E.M. Heinsbroek, Juan J. Garcia-Vallejo, Jan Verhoeff, Wouter J. de Jonge, Andrew Y. F. Li Yim, Matthew J Bell, Huw D. Lewis, Manon E. Wildenberg, Iris Admiraal, Rab K. Prinjha, Rebecca C. Furze, Richard Gregory, Mohammed Ghiboub, Palwinder K. Mander, Inmaculada Rioja, Manon de Krijger, Olaf Welting, Shafaque Rahman

Publikováno v: Elfiky, A M I, Ghiboub, M, Li Yim, A Y F, Hageman, I L, Verhoeff, J, de Krijger, M, van Hamersveld, P H P, Welting, O, Admiraal, I, Rahman, S, Garcia-Vallejo, J J, Wildenberg, M E, Tomlinson, L, Gregory, R, Rioja, I, Prinjha, R K, Furze, R C, Lewis, H D, Mander, P K, Heinsbroek, S E M, Bell, M J & de Jonge, W J 2022, ' Carboxylesterase-1 Assisted Targeting of HDAC Inhibitors to Mononuclear Myeloid Cells in Inflammatory Bowel Disease ', Journal of Crohn's and Colitis, vol. 16, no. 4, pp. 668-681 . https://doi.org/10.1093/ecco-jcc/jjab176
Journal of Crohn's and Colitis, 16(4), 668-681. Elsevier
Journal of Crohn's & colitis, 16(4), 668-681. Elsevier

Background and AimsHistone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aim

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::082c0316620861e7964614f67286a50a
https://doi.org/10.1093/ecco-jcc/jjab176