Click chemistry enables preclinical evaluation of targeted epigenetic therapies
| Autor: | Aoife Ward, Dean Tyler, Sarah-Jane Dawson, Edwin D. Hawkins, Paola Grandi, Dave Lugo, Johanna Vappiani, Richard Gregory, Anna Rutkowska, Tatiana Cañeque, Susan Jackson, Cesar Ramirez Molina, Antje Hienzsch, Anne J. Wagner, Rab K. Prinjha, Mark A. Dawson, Thilo Werner, Neil Stuart Garton, Charles C. Bell, Christopher Roland Wellaway, Omer Gilan, Colin M. House, Margarida Figueiredo, Yih-Chih Chan, Gerard Drewes, Raphaël Rodriguez, Laura MacPherson, Sabine Stolzenburg, Enid Y.N. Lam |
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| Rok vydání: | 2017 |
| Předmět: |
Epigenomics
0301 basic medicine BRD4 Computational biology Biology 010402 general chemistry Proteomics Bioinformatics 01 natural sciences Article Benzodiazepines Mice 03 medical and health sciences Drug Delivery Systems In vivo Animals Tissue Distribution Epigenetics Precision Medicine Cells Cultured Leukemia Multidisciplinary 0104 chemical sciences 3. Good health Chromatin Bromodomain Disease Models Animal 030104 developmental biology Click chemistry Click Chemistry Transcription Factors |
| Zdroj: | Science |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Are better drugs just a click away? Drugs that show promise in preclinical models often fail in the clinic, in part because of limited information on drug localization within cells and across tissues. In a proof-of-concept study, Tyler et al. applied click chemistry methods to study the localization of bromodomain inhibitors. These are cancer drugs that alter chromatin structure and gene expression. Clickable derivatives of the drugs localized within chromatin and showed that the drugs exhibit distinct modes of binding at responsive and unresponsive genes. In a mouse leukemia model, the click-probes revealed that the drugs accumulate to different extents in the spleen and bone marrow, which are two tissue sources of leukemic cells. Science , this issue p. 1397 |
| Databáze: | OpenAIRE |
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