Sapacitabine

Sapacitabine is an orally available nucleoside analog prodrug that is structurally related to cytarabine. IC50 & Target: nucleoside analog^[1] In Vitro: Concentrations of Sapacitabine required to achieve an IC₅₀ 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 G₂/M phase. L1210 cells with deoxycytidine kinase (dCK) activity are sensitive to Sapacitabine, (IC₅₀ 20±6 μM). In the docetaxel/Sapacitabine combinations, synergistic effects (CI<1) are observed when docetaxel is given before Sapacitabine in both cell lines^[1]. In Vivo: On Day 14, the Sapacitabine (5?mg/kg)+vorinostat (33?mg/kg) group has a mean tumour volume of 245?mm³ 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?mm³ and a TGI of 112%^[2].