Description
Sapacitabine is an orally available nucleoside analog proagent that is structurally related to cytarabine.In VitroConcentrations of Sapacitabine required to achieve an IC 50 range from 3±0.6 µM for the colon cancer cell line HCT116 to 67±14 µM for the breast cancer cell line MDA-MB-435. Cell cycle analysis shows that 35% Sapacitabine-treated cells are arrested in late-S phase and 41% in G 2 /M phase. L1210 cells with deoxycytidine kinase (dCK) activity are sensitive to Sapacitabine, (IC 50 20±6 µM). In the docetaxel/Sapacitabine combinations, synergistic effects (CI<1) are observed when docetaxel is given before Sapacitabine in both cell lines. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoOn Day 14, the Sapacitabine (5 mg/kg)+vorinostat (33 mg/kg) group has a mean tumour volume of 245 mm 3 and a tumour growth inhibition (TGI) of 92%, whereas the Sapacitabine (15 mg/kg)+vorinostat (33 mg/kg) group has a mean tumour volume of 107 mm 3 and a TGI of 112%. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal administrationFemale (nu/nu) mice are injected subcutaneously with 1×10 7 MV4-11 cells resuspended in 50% Matrigel at a single site on their flanks. Once tumour volumes are 126 to 256 mm 3 (16 days post-implantation) animals are pair matched by tumour size into treatment groups (minimum of six mice per group) with a mean tumour size of ~190 mm 3. Tumour measurements are calculated using the formula: volume (mm 3 )=width 2 (mm)×length (mm)×0.5. Sapacitabine is administered once a day orally (5 or 15 mg/kg) for 4 days, followed by a 3-day break before another 4 days of treatment; dosing starts on the same day as distribution to the treatment groups. aladdin has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:nucleoside analog