Small molecule inhibitors targeting DNA repair pathways in cancer cells is a novel and promising approach in cancer therapy, which can improve current therapeutic regimen. Although various attempts have been made for designing inhibitors against DNA damage response and repair proteins, reports on Nonhomologous End Joining (NHEJ) inhibitors are limited. Of the several chemical moieties identified, SCR7 and its oxidized form are novel and potent DNA Ligase IV inhibitors involved in the abrogation of DNA end joining thereby leading to cell death. In the present study, we have synthesized sodium salt of SCR7 to generate a water-soluble version of the molecule, referred to as water-soluble SCR7 (WS-SCR7). WS-SCR7 inhibits NHEJ in Ligase IV dependent manner, with a subtle effect on Ligase III at higher concentration. No effect on Ligase I mediated joining was observed. WS-SCR7 shows cytotoxicity in cancer cell lines, leading to induction of apoptosis in a dose-dependent manner.