Sapacitabine (CS682) is an orally available nucleoside analog precursor compound with potential anti-tumor activity for the study of acute myeloid leukemia.

Sapacitabine对结肠癌细胞株 HCT116 和乳腺癌细胞株 MDA-MB-435 的 IC50 值分别为 3 ± 0.6 µM 和 67 ± 14 µM。细胞周期分析表明，经Sapacitabine处理的细胞中有 35% 停滞在 S 期晚期，41% 停滞在 G2/M 期。Sapacitabine对具有脱氧胞苷激酶（dCK）活性的 L1210 细胞敏感（IC50 20±6 μM）[1]。

第14天，Sapacitabine（5 mg/kg）+vorinostat（33 mg/kg）组的平均肿瘤体积为245 mm3，肿瘤生长抑制（TGI）为92%，而Sapacitabine（15 mg）组 /kg）组，平均肿瘤体积为245mm3，肿瘤生长抑制（TGI）为92%； +vorinostat（33 mg/kg）组的平均肿瘤体积为107mm3，TGI为112%[2]。

A panel of the colon (HT29, HCT116, COLO205, HCC2998), breast (MCF7, MDA-MB-435), lung (HOP62, HOP92), ovarian (OVCAR3, IGROV1) cancer cell lines are used in this study. The cell cycle stage and percentage of apoptotic cells are assessed by flow cytometry. In brief, cells are seeded in 25 cm3 flasks and are untreated or treated with various concentrations of Sapacitabine. At the indicated time points, adherent and non-adherent cells are collected, washed with PBS, fixed in 70% ethanol and stored at 4°C until use. Cells are rehydrated in PBS, incubated for 20?min at room temperature (25°C) with 250?μg/mL RNAse A with Triton X-100 and 20?min at 4°C with 50?μg/mL propidium iodide in the dark. The cell cycle distribution and percentage of apoptotic cells are determined with a flow cytometer and analysed by FACS Calibur [1].

Female (nu/nu) mice are injected subcutaneously with 1×107 MV4-11 cells resuspended in 50% Matrigel at a single site on their flanks. Once tumour volumes are 126 to 256?mm3 (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?mm3. Tumour measurements are calculated using the formula: volume (mm3)=width2 (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 [2].