Figure S2.
HIFi concentration–dependent in vitro and dose-dependent in vivo effects. (A) To calculate IC50 values shown in Fig. 3 P, cancer cell lines were exposed to vehicle or HIFi at the indicated concentrations for 24 h at 1% O2, and expression of mRNA encoding the indicated HIF target gene mRNA was analyzed by RT-qPCR (mean + SD, n = 3). (B) Dose escalation study of HIFi SS1.21 or SS3.2 was performed. Two IP doses (indicated in mg/kg) 12 h apart were administered (n = 3 mice each). Doses marked in green were well tolerated, whereas doses marked in pink led to decreased physical activity and/or unsteady gait in the first hour after administration. (C) Mice were administered vehicle or HIFi for 15 days as indicated, and BW was measured (mean + SD, n = 3) every 2–3 days. (D) Dose escalation study of HIFi 1.21S9N or 3.2.16 was performed. Two IP doses (indicated in mg/kg) 12 h apart were administered (n = 3 mice each). Doses marked in green were well tolerated, whereas doses marked in pink led to decreased physical activity and/or unsteady gait in the first hour after administration. (E) BW was measured after the second dose (mean + SD, n = 3). Refer to the image caption for details. The image contains multiple graphs and charts illustrating the effects of H I F i on cancer cell lines and mice. Panel A shows bar graphs representing the relative m R N A expression levels of various H I F target genes in different cancer cell lines after exposure to different concentrations of H I F i for 24 hours at 1 percent O 2. The I C 50 values for each cell line are indicated. Panel B displays a dose escalation study of H I F i S S 1.21 or S S 3.2, with doses marked in green indicating well-tolerated levels and doses marked in pink indicating levels that led to decreased physical activity and/or unsteady gait. Panel C presents a line graph showing the body weight of mice administered vehicle or H I F i for 15 days, measured every 2-3 days. Panel D shows another dose escalation study of H I F i 1.21 S 9 N or 3.2.16, with similar color coding for tolerated and non-tolerated doses. Panel E depicts a line graph of body weight measured after the second dose. Each graph includes mean values with standard deviation bars, and the number of replicates is specified. All data is approximate.

HIFi concentration–dependent in vitro and dose-dependent in vivo effects. (A) To calculate IC50 values shown in Fig. 3 P, cancer cell lines were exposed to vehicle or HIFi at the indicated concentrations for 24 h at 1% O2, and expression of mRNA encoding the indicated HIF target gene mRNA was analyzed by RT-qPCR (mean + SD, n = 3). (B) Dose escalation study of HIFi SS1.21 or SS3.2 was performed. Two IP doses (indicated in mg/kg) 12 h apart were administered (n = 3 mice each). Doses marked in green were well tolerated, whereas doses marked in pink led to decreased physical activity and/or unsteady gait in the first hour after administration. (C) Mice were administered vehicle or HIFi for 15 days as indicated, and BW was measured (mean + SD, n = 3) every 2–3 days. (D) Dose escalation study of HIFi 1.21S9N or 3.2.16 was performed. Two IP doses (indicated in mg/kg) 12 h apart were administered (n = 3 mice each). Doses marked in green were well tolerated, whereas doses marked in pink led to decreased physical activity and/or unsteady gait in the first hour after administration. (E) BW was measured after the second dose (mean + SD, n = 3).

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