Sapacitabine is a chemotherapeutic drug developed by American biotechnology firm Cyclacel undergoing clinical trials of its effectiveness against leukemia.Sapacitabine is unique in that it is an orally available nucleoside analog prodrug of CNDAC that acts through a dual mechanism. As a prodrug, it exhibits the therapeutic effect upon being metabolized; CNDAC lasts longer in the bloodstream by being metabolized from sapacitibine than by being directly administered. The compound interferes with DNA synthesis by causing single-strand DNA breaks due to CNDAC being incorporated into DNA during replication or repair, then inducing arrest of the cell division cycle at G2 phase.
Both sapacitabine and its major metabolite, CNDAC, have demonstrated potent anti-tumor activity in both blood and solid tumors in preclinical studies. In a liver metastatic mouse model, sapacitabine was shown to be superior to gemcitabine (Gemzar; Lilly) or 5-FU, two widely used nucleoside analogs, in delaying the onset and growth of liver metastasis.