DNA ligase IV seals double-strand breaks during the process of nonhomologous end-joining in DNA repair. Inhibiting this function in cancer cells is one strategy to prevent deleterious cell growth. SCR7 pyrazine is a small molecule inhibitor of DNA ligase IV that prevents nonhomologous end-joining by interfering with ligase binding and activating apoptosis. It also inhibits ligase III, but does not affect the activity of T4 DNA ligase or ligase I. SCR7 pyrazine has been used to increase the rate of homology directed repair triggered by DNA double-strand breaks and to inhibit cancer cell growth in vitro (IC50s = 8-120 μM) and in mouse models when co-administered with double-strand break-inducing therapeutic compounds.
