L189 (CAS 64232-83-3)

L189 functions as a potent inhibitor targeting DNA ligases I, III, and IV, with half-maximal inhibitory concentrations (IC50) of 5, 9, and 5 µM respectively, demonstrating its efficacy in obstructing the activities of these critical enzymes involved in DNA repair and replication processes. It exhibits a pronounced affinity for DNA ligase I, with a binding constant (Ki) of 5 µM, indicating a strong inhibitory interaction that blocks the enzyme′s ability to bind DNA. L189 is particularly effective in disrupting the second step of the DNA ligation reaction, a pivotal phase where the DNA nick is sealed, thereby impeding the ligation process essential for DNA repair and replication continuity. Its mechanism of action is further highlighted by its ability to inhibit two fundamental pathways of DNA repair: base excision repair (BER), a key mechanism for repairing small lesions without altering the overall DNA structure, and non-homologous end joining (NHEJ), a critical pathway for repairing double-strand breaks.