SCR7 pyrazine also is a potent inhibitor of nonhomologous endjoining (NHEJ) mediated by DNA ligase IV. It enhances CRISPR-Cas9-mediated homology-directed repair (HDR) efficiency in vitro upt to 19-fold. SCR7 pyrazine is a product of spontaneous cyclization of CRISPR enhancer SCR7 first reported by Srivastava, M., et al.
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 is a small molecule inhibitor of DNA ligase IV that prevents nonhomologous end-joining by interfering with ligase binding and activating apoptosis.1 It also inhibits ligase III, but does not affect the activity of T4 DNA ligase or ligase I. SCR7 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.1,2,3,4
