(a) Kinetics of platelet reduction and
rebound following a single
IP dose of A-1155463 in SCID-Beige mice. Nontumor bearing female SCID-Beige
mice were treated with a single dose of A-1155463 (5 mg/kg, IP). Blood
samples were collected by means of retro-orbital bleeds at regular
time intervals. The number of platelets was plotted as a function
of time. Each point reflects the average of 5 biological replicates.
Each box indicates the median ± SEM. The error bars reflect minimum
and maximum values (n = 5 per time point). The colored
boxes represent upper and lower quartiles. The horizontal lines within
each colored box represent the mean, and the whiskers are the upper
and lower range. (b) Inhibition of H146 SCLC xenograft growth by A-1155463.
Female SCID-Beige mice bearing NCI-H146 subcutaneous xenografts were
treated with A-1155463 (5 mg/kg IP, QDx14) or an equal volume of the
vehicle (5% DMSO, 10% EtOH, 20% Cremophor ELP, and 65% D5W; n = 5 per time point) and changes in tumor volume determined
as a function of time. Each point reflects the average volume of 5
tumors. Points with significant (Student’s t test, p < 0.05) difference between treated and
untreated groups are indicated by means of asterisks. Tumor volume
was calculated by W2·L·0.5 where W and L are two perpendicular diameters indicating
width and length, respectively.