1. Selective targeting of BD1 and BD2 of the BET proteins in cancer and immuno-inflammation
- Author
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Peter Ernest Soden, Emma J. Roberts, Danette L. Daniels, Chun-wa Chung, Stephen John Atkinson, Paul Bamborough, Anne Marie Michon, Johanna Vappiani, Andrea C. Haynes, Massimo Petretich, Marcus Bantscheff, Miriam M. Yeung, Matthew J Bell, Sarah-Jane Dawson, Paola Grandi, Dane Vassiliadis, Simon Taylor, James Gray, Omer Gilan, Kathy Knezevic, Marjeta Urh, Matthew J Lindon, Marian L. Burr, Rab K. Prinjha, Alex Preston, Inmaculada Rioja, Mark A. Dawson, Gerard Drewes, Thilo Werner, Christopher Roland Wellaway, Emmanuel Hubert Demont, Anna K. Bassil, Nicola Harker, Thomas Gobbetti, Enid Y.N. Lam, David F. Tough, and Vinod Kumar
- Subjects
Regulation of gene expression ,Male ,BRD4 ,Multidisciplinary ,Chromatin binding ,HEK 293 cells ,Prostatic Neoplasms ,Proteins ,Biology ,Article ,Chromatin ,Bromodomain ,Protein Domains ,Gene expression ,Cancer research ,Humans ,Transcription factor - Abstract
Bromodomain inhibitors revisited Bromodomain and extraterminal domain (BET) proteins contribute to the pathogenesis of cancer and immune diseases through their effects on transcriptional regulation. BET proteins contain two nearly identical bromodomains, BD1 and BD2, structural modules that have attracted great interest as targets for drug development. First-generation drugs that inhibited both BD1 and BD2 showed promising therapeutic activity in preclinical models but proved to be less efficacious in clinical trials. Gilan et al. took a different approach and designed drugs that selectively inhibited BD1 or BD2 (see the Perspective by Filippakopoulos and Knapp). They found that BD1 and BD2 inhibitors altered gene expression in different ways and that BD2 inhibitors had greater therapeutic activity than BD1 inhibitors in preclinical models of inflammation and autoimmune disease. Science , this issue p. 387 ; see also p. 367
- Published
- 2020