Research Paper Volume 8, Issue 5 pp 958—973

Figure 3. FS-115 shows excellent pharmacokinetic features. (A) Graph reports the pharmacokinetic profile of FS-115 in male CD-1 mice, looking at plasma profiles following a single dose of FS-115, via both intravenous (IV, 2 mg/kg) and oral (OS, 10 mg/kg) routes of administration. Plasma was sampled at 8 time points (n=3 mice per time point, terminal sampling) over 24 hours. FS-115 was determined to exhibit an oral bioavailability in excess of 95%, an IV half-life of 0.83 hr, clearance of 25 ml/min/kg and a volume of distribution of 1.64 L. (B) Graph reports the brain-penetrance of FS-115 in male CD-1 mice, following a single dose of FS-115, given orally (p.o.) at 25 mg/kg. Plasma and brain were sampled at 3 time points (0.5, 1.1 and 2.6 hr). (C) Graph reports the pharmacodynamic profile of FS-115 in nude mice orthotopically implanted with MDA-MB-231 cells and treated with either vehicle QD x 3 PO or FS-115 125 mg/kg BID x 3 PO (6 doses in total). Twelve hours after the final dose animals were sacrificed, tumors resected and homogenized and ELISA for phospho-S6, total S6, phospho-AKT and total AKT. Data are normalized by the expression of the respective total protein. Differences were considered significant when p<0.05 (*) and calculated by two tailed t-test.