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10.1126/science.aal2066

http://scihub22266oqcxt.onion/10.1126/science.aal2066
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C5865750!5865750!28619718
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suck abstract from ncbi


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pmid28619718      Science 2017 ; 356 (6345): 1397-401
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  • Click chemistry enables preclinical evaluation of targeted epigenetic therapies #MMPMID28619718
  • Tyler DS; Vappiani J; Cañeque T; Lam EYN; Ward A; Gilan O; Chan YC; Hienzsch A; Rutkowska A; Werner T; Wagner AJ; Lugo D; Gregory R; Molina CR; Garton N; Wellaway CR; Jackson S; MacPherson L; Figueiredo M; Stolzenburg S; Bell CC; House C; Dawson SJ; Hawkins ED; Drewes G; Prinjha RK; Rodriguez R; Grandi P; Dawson MA
  • Science 2017[Jun]; 356 (6345): 1397-401 PMID28619718show ga
  • 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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