Abstract / Description of output
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.
Original language | English |
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Journal | Bioorganic & Medicinal Chemistry Letters |
Early online date | 17 Aug 2015 |
DOIs | |
Publication status | Published - 1 Oct 2015 |
Keywords / Materials (for Non-textual outputs)
- DNA Repair
- ERCC1-XPF
- Catechol
- 3-Hydroxypyridone
- Cisplatin potentiation