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Tyler, Dean S.; Vappiani, Johanna; Cañeque, Tatiana; Lam, Enid Y. N.; Ward, Aoife; Gilan, Omer; Chan, Yih-Chih; Hienzsch, Antje; Rutkowska, Anna; Werner, Thilo; Wagner, Anne J.; Lugo, Dave; Gregory, Richard; Molina, Cesar Ramirez; Garton, Neil; Wellaway, Christopher R.; Jackson, Susan; MacPherson, Laura; Figueiredo, Margarida; Stolzenburg, Sabine; Bell, Charles C.; House, Colin; Dawson, Sarah-Jane; Hawkins, Edwin D.; Drewes, Gerard; Prinjha, Rab K.; Rodriguez, Raphaël; Grandi, Paola; Dawson, Mark A.
Science (American Association for the Advancement of Science), 06/2017, Letnik: 356, Številka: 6345Journal Article
The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click chemistry and can be used as molecular probes in vitro and in vivo. We used click proteomics and click sequencing to explore the gene regulatory function of BRD4 (bromodomain containing protein 4) and the transcriptional changes induced by BET inhibitors. In our studies of mouse models of acute leukemia, we used high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the preclinical assessment of a wide range of drugs.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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