Figure 4. Compound 8.12 displays higher potency than cysmethynil in tumor growth inhibition in vivo. (A) Plasma concentrations of compound 8.12 in treated mice. Left: Compound 8.12 was administered at 10mg/kg (●) and 25 mg/kg (■) intraperitoneally, and plasma drug concentrations at time points up to 8 h were determined as described in Materials and Methods. The horizontal line indicates the plasma drug concentration that is approximately equivalent to the in vitro IC₅₀ of compound 8.12 for HepG2 cells. Each data point was obtained from 3 animals (n = 3). Right: Table shows the pharmacokinetic parameters of compound 8.12. AUC, area under the time-concentration curve. (B) Mice bearing tumor xenografts were treated with: ●, vehicle only; ▲, cysmethynil 75 mg/kg; ▼, compound 8.12 30 mg/kg, and the volumes of the tumors were measured as described in Materials and Methods. The volumes of the tumors up to 24 d post-treatment were plotted as mean ± SEM P ≤ 0.05 (*). Each treatment group consists of 8 animals (n = 8). (C) The tumors from the study in (B) were harvested and weighed at the end of the study period; the mean ± SD is plotted as shown. P ≤ 0.05 (*). Similar experiments were conducted three times with similar results.