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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.
Afiliação
  • Chapman TM; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Gillen KJ; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Wallace C; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Lee MT; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Bakrania P; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Khurana P; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Coombs PJ; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Stennett L; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Fox S; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Bureau EA; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Brownlees J; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
  • Melton DW; MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
  • Saxty B; Centre for Therapeutics Discovery, MRC Technology, 1-3 Burtonhole Lane, Mill Hill, London NW7 1AD, UK.
Bioorg Med Chem Lett ; 25(19): 4097-103, 2015 Oct 01.
Article em En | MEDLINE | ID: mdl-26318993
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridonas / Catecóis / Proteínas de Ligação a DNA / Reparo do DNA / Endonucleases Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridonas / Catecóis / Proteínas de Ligação a DNA / Reparo do DNA / Endonucleases Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article