Virtual Screening and Biological Evaluation of Inhibitors Targeting the XPA-ERCC1 Interaction

• DOI: 10.1371/journal.pone.0051329
• Publication Date: 2012-12-14T17:28:47Z
• Authors: Khaled H. Barakat; Lars P. Jordheim; Rolando Perez-Pin...; David Wishart; Charles Dumontet; Jack A. Tuszynski
• Keywords: ERCC1

Background Nucleotide excision repair (NER) removes many types of DNA lesions including those induced by UV radiation and platinum-based therapy. Resistance to therapy correlates with high expression ERCC1, a major element the NER machinery. The interaction between ERCC1 XPA is essential for successful function. Therefore, one way regulate inhibiting activity XPA. Methodology/Principal Findings Here we continued our earlier efforts aimed at identification characterization novel inhibitors ERCC1-XPA interaction. We used refined virtual screening approach combined biochemical biological evaluation compounds their ability interact sensitize cells radiation. Our findings reveal new validated inhibitor that significantly sensitized colon cancer indicating strong inhibition Conclusions factor in acquiring resistance Regulating pathway has potential improving efficacy platinum treatments. One followed inhibit two elements, Here, performed against identified block XPA-ERCC1 binding.