Figure 4. 1t is well tolerated and displays excellent PK/PD characteristics.
(A) PK profiles of 1t administered by i.v. injection or p.o. gavage to mice. The dotted line represents the average GI50 value for BRAF mutant tumors (Fig 2A). (B) Mice bearing WM266.4 xenografts received a single p.o. dose of vehicle or 1t (20 mg/kg) and tumors were harvested at the indicated times. Tumor lysates were analyzed by quantitative fluorescent Western blotting for MEK phosphorylation and total MEK1. The level of MEK phosphorylation was normalized to the amount of detectable MEK1. (C) Mice were treated with 10 or 20 mg/kg/d 1t p.o. for 4 d (indicated by Δ) and body weight was monitored for a further 27 d. Mean body weight as a percentage of vehicle-treated animals is plotted ± SEM (n=2 mice per group).