Pre-clinical activity of TM5441 <i>in vivo</i>.

<p><b>A</b>. Individual tumor volume was plotted over time (days) for vehicle and TM5441 (20 mg/kg/day) treated mice (n = 5 per group). <b>B</b>. Average time (±SD) to reach maximal tumor growth for vehicle and TM5441-treated mice was plotted over time (days). <b>C</b>. Average tumor relative luciferase units (RLUs) (±SD) for mice treated with vehicle or TM5441 was plotted over time (days). <b>D</b>. Mouse survival (%) was plotted for mice treated with vehicle (black line) or TM5441 (red line) over time (days). <b>E</b>. Representative histology sections of tumors stained with H&E. Yellow arrows indicate the area selected for the inset panels. Blue arrows indicate hemorrhagic areas with red blood cells. Green arrows indicate EC lining the vessels. Scale bar = 50 μm. <b>F</b>. Representative histological sections of tumors stained for CD31 (red) as described in Materials and Methods and counterstained with nuclear 4’6’-diamidino-2-phenylindole (DAPI) (blue) staining. Yellow arrows indicate the area selected for the inset panels. White arrows indicate CD31 positive cells lining the vessel wall. Clear arrows with a white outline indicate the absence of distinct CD31 positive cells. The graph shows the percentage of CD31 positive staining (± SD, n = 5 tumors per group with 5 sections per tumor, n = 25 total per group). Scale bar = 50 μm. <b>G</b>. Representative histology sections of tumors stained with TUNEL as described in Materials and Methods. TUNEL staining (brown) counterstained with methyl green (green). Yellow arrows indicate the area selected for the inset panels. Red arrows indicate TUNEL positive cells. The graph shows the average TUNEL optical density (± SD, n = 5 tumors per group with 5 sections per tumor, n = 25 total per group). Scale bar = 50 μm. * indicates <i>P</i> values compared to vehicle control < 0.05, and *** indicates <i>P</i> < 0.001.