产品描述:
SW044248 is a DNA topoisomerase I inhibitor that exhibits selective cytotoxicity across a panel of 46 non-small cell lung cancer cell (NSCLC) lines (IC50s = ~2 μM for HCC4017, H292, and H1819 cells versus >20 μM for the remaining cell lines).{37220} It induces cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 and blocks DNA replication, RNA transcription, and protein translation in HCC4017 susceptible-, but not HBEC30KT resistant-, cells in a dose-dependent manner. SW044248 inhibits the ability of recombinant topoisomerase 1 to relax supercoiled DNA in a dose-dependent manner and topoisomerase 1 knockdown rescues HCC4017 cells from SW044248 cytotoxicity. SW044248 is less cytotoxic against HCC4017 cells transfected with CDKN1, a protein overexpressed in SW044248-resistant NSCLC cells, indicating a role for CDKN1A in SW044248 resistance.