53527-20-1Relevant academic research and scientific papers
Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF
Chapman, Timothy M.,Gillen, Kevin J.,Wallace, Claire,Lee, Maximillian T.,Bakrania, Preeti,Khurana, Puneet,Coombs, Peter J.,Stennett, Laura,Fox, Simon,Bureau, Emilie A.,Brownlees, Janet,Melton, David W.,Saxty, Barbara
supporting information, p. 4097 - 4103 (2015/11/03)
Catechol-based inhibitors of ERCC1-XPF endonuclease activity were identified from a high-throughput screen. Exploration of the structure-activity relationships within this series yielded compound 13, which displayed an ERCC1-XPF IC50 of 0.6 μM, high selectivity against FEN-1 and DNase I and activity in nucleotide excision repair, cisplatin enhancement and γH2AX assays in A375 melanoma cells. Screening of fragments as potential alternatives to the catechol group revealed that 3-hydroxypyridones are able to inhibit ERCC1-XPF with high ligand efficiency, and elaboration of the hit gave compounds 36 and 37 which showed promising ERCC1-XPF IC50 values of 10 μM.
