L82 is a selective and uncompetitive DNA ligase 1 (DNA Lig1) inhibitor (hLig1 IC50=12 μM). L82 shows anti-proliferative activity to breast cancer cells[1][2].
L82 (0-50 μM; 6 d) shows anti-proliferative activity to breast cancer cells[2].
L82 (50 μM; 0-48 h) shows cytostatic activity due to activation of the G1/S checkpoint in MCF7 cells[2].
Cell Proliferation Assay[2]
| Cell Line: | MCF10A, MCF7, HCT116, and HeLa cells |
| Concentration: | 0-50 μM |
| Incubation Time: | 6 days |
| Result: | Reduced the proliferation of a normal breast epithelial cell line MCF10A and the breast cancer cell lines MCF7, HeLa and HCT116, in a concentration-dependent manner. |
Cell Cycle Analysis[2]
| Cell Line: | MCF7 cells |
| Concentration: | 50 μM |
| Incubation Time: | 0-48 hours |
| Result: | Showed a transient accumulation of cells at G2/M after 12 h, then showed an accumulation at G0/G1 that peaked after 24 h. Decreased in the S phase cell in accompany with the increase in the G0/G1 phase. |
[1]. Howes TRL, et al. Structure-activity relationships among DNA ligase inhibitors: Characterization of a selective uncompetitive DNA ligase I inhibitor. DNA Repair (Amst). 2017 Dec;60:29-39.
[2]. Chen X, et al. Rational design of human DNA ligase inhibitors that target cellular DNA replication and repair. Cancer Res. 2008 May 1;68(9):3169-77.