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. Author manuscript; available in PMC: 2017 Jul 6.
Published in final edited form as: Nature. 2016 Sep 5;539(7627):107–111. doi: 10.1038/nature19795

Figure 3.

Figure 3

PT2399 pharmacodynamic effects in vivo. a, b Light emission, normalized to total cellular protein (a) and cell number (b) in 786-O 3XHRE-Luc reporter cells expressing VHL or an empty vector (Vec). The cells were treated with PT2399 overnight (a) or at 2 μM for the indicated durations (b). 1 mM DMOG was included in (a) as a control; n=3. c, Luc values of 786-O derivatives expressing Luc driven by the indicated promoters and then exposed to either PT2399 or to 1 mM DMOG; n=3 biological replicates. d, Representative bioluminescent images (BLI) of mice with orthotopic tumors formed by 786-O 3XHRE-Luc reporter cells (left kidney) or 786-O CMV-Luc reporter cells (right kidney). Images were obtained before and after two days of PT2399 30 mg/kg given twice daily (n=6 mice from two independent experiments) or vehicle (n=6 mice from two independent experiments) by oral gavage. e, f, Quantification of BLI from mice as in (d); n=4 mice from two independent experiments. Values were normalized to the pretreatment values for each treatment. g, Serial BLI of a mouse as in (d) treated with PT2399 (blue arrows). Shown on the y-axis are absolute photon counts for the 3XHRE-Luc tumor. Data as mean ± s.e.m. (a–c, e and f). Statistical significance was assessed using Mann-Whitney tests (f).