AR-42 shows <i>in vivo</i> efficacy in multiple models of B-cell malignancy.

<p>(<b>A</b>) SCID mice were engrafted with two million Raji cells via tail vein injection. Starting 3 days post-inoculation, mice were treated by oral gavage with vehicle only daily (n = 11), vorinostat at the maximum tolerated dose of 50 mg/kg daily (n = 5), and AR-42 at 75 mg/kg (n = 6) Monday, Wednesday and Friday. The median survival advantage in the AR-42 group relative to the vehicle control group was significant (p = 0.001). (<b>B</b>) SCID mice were engrafted with forty million JeKo-1 cells via tail vein injection. Starting on day 15 post-inoculation, mice were treated intraperitoneally with vehicle alone or 20 mg/kg AR-42 every three days (n = 5 per group). The improvement in median survival relative to control was significant (p = 0.003). (<b>C</b>) SCID mice were engrafted with one million Eμ-Tcl1 leukemia cells via tail vein injection. When the circulating leukocyte count averaged 20,000 cells/µL across the group (dashed horizontal line; 69 days post-inoculation), mice were randomized to two cohorts and treated Monday, Wednesday and Friday for two weeks with vehicle only (light bars) or with AR-42 at 75 mg/kg via oral gavage (dark bars) (n = 5, both groups). *The decrease in circulating leukocytes in AR-42 treated mice vs. controls at week 12 relative to week 10 was significant (p = 0.0007). (<b>D</b>) Animals in (<b>C</b>) were followed for survival (n = 5 per group). The increase in median survival in the AR-42 group relative to control was significant (p = 0.025).