AMG 900 inhibits p-Histone H3 and increases the percentage of G
M cells in a dose-dependent manner in COLO 205 tumors and mouse bone marrow measured by Flow Cytometry (FCM). Mice bearing established tumors were orally administered a single dose of vehicle alone or AMG 900 at 3.75, 7.5, or 15 mg/kg. Bone marrow and tumor specimens were collected three hours after treatment (n = 10 per treatment group) and processed for p-Histone H3 and DNA content analysis by FCM. (A) Representative cell cycle profiles of bone marrow (upper panel) and tumor (lower panel, COLO 205 tumor cells were identified using an anti-cytokeratin antibody). AMG 900 treatment decreases the p-Histone H3 positive cell population in G2M detectable in the vehicle-treated control (blue, arrow). Column graphs represent the percentage of p-Histone H3 positive G2M cells (B and C) and G2M cells (D and E) for each treatment group (mean + SE). Statistical significance was determined by comparing the individual AMG 900 treatment groups with vehicle-treated control (*P <0.0001).