Description
L189 is a competitive inhibitor of DNA ligases I, III, and IV (IC50s = 5, 9, and 5 μM, respectively). It blocks DNA binding (Ki = 5 μM for DNA ligase I), increasing the cytotoxicity of DNA-damaging agents, including ionizing radiation. L189 preferentially inhibits the interaction of the ligase with damaged DNA, inhibiting base excision repair and non-homologous end-joining.
Uses
L189 has been shown to inhibit DNA ligases I, III, and IV and may have potential use in the development of anticancer agents.
References
[1]. xi chen, shijun zhong, xiao zhu, et al. rational design of human dna ligase inhibitors that target cellular dna replication and repair. cancer res., 2008, 68(9): 3169-3177.
[2]. mark r. taylor, john a. conrad, daniel wahl, et al. kinetic mechanism of human dna ligase i reveals magnesium-dependent changes in the rate-limiting step that compromise ligation efficiency. journal of biological chemistry, 2011, 286(26): 23054-23062.
[3]. christian jekimovs, emma bolderson, amila suraweera, et al. chemotherapeutic compounds targeting the dna double-strand break repair pathways: the good, the bad, and the promising. frontiers in oncology, 2014, 4: article 86.
