Publications

Publications

Small Molecule Inhibitors of ERCC1-XPF Protein-Protein Interaction Synergize Alkylating Agents in Cancer Cells

By:
Contributors: Jack Tuszynski Research Group
Mol Pharmacol. 2013 Jul;84(1):12-24. doi: 10.1124/mol.112.082347. Epub 2013 Apr 11.

Abstract

The benefit of cancer chemotherapy based on alkylating agents is limited because of the action of DNA repair enzymes, which mitigate the damage induced by these agents. The interaction between the proteins ERCC1 and XPF involves two major components of the nucleotide excision repair pathway. Here, novel inhibitors of this interaction were identified by virtual screening based on available structures with use of the National Cancer Institute diversity set and a panel of DrugBank small molecules. Subsequently, experimental validation of the in silico screening was undertaken. Top hits were evaluated on A549 and HCT116 cancer cells. In particular, the compound labeled NSC 130813 [4-[(6-chloro-2-methoxy-9-acridinyl)amino]-2-[(4-methyl-1-piperazinyl)methyl]] was shown to act synergistically with cisplatin and mitomycin C; to increase UVC-mediated cytotoxicity; to modify DNA repair as indicated by the staining of phosphorylated H2AX; and to disrupt interaction between ERCC1 and XPF in cells. In addition, using the Biacore technique, we showed that this compound interacts with the domain of XPF responsible for interaction with ERCC1. This study shows that small molecules targeting the protein-protein interaction of ERCC1 and XPF can be developed to enhance the effects of alkylating agents on cancer cells.

 

PubMed

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Dr. John Lewis recognized for a breakthrough innovation with commercial application: ClarityDX Prostate

Alberta’s life sciences industry association; BioAlberta, hosted its 2018 awards gala in Calgary, September 24. BioAlberta honoured Dr. John Lewis, the Frank and Carla Sojonky Chair in Prostate Cancer Research and an Associate Professor at the University of Alberta, with its Scientific Achievement and Innovation Award.

The Scientific Achievement and Innovation award recognizes an individual or a team responsible for a breakthrough innovation with commercial application. John Lewis and his research team based with his spin-off company Nanostics Inc. developed ClarityDX Prostate, a blood test designed to accurately diagnose aggressive prostate cancer. ClarityDX Prostate will give clinicians and physicians another tool to help them and their patients decide to perform a biopsy, or not. When the test becomes commercially available it is expected to reduce the number of prostate biopsies by 50%.

BioAlberta also gave out The Company of the Year award to Circle Cardiovascular Imaging Inc. for significant achievement within the marketplace and Alberta’s business community. It has developed technology to produce an innovative post-processing cardiovascular imaging solution to improve patient outcomes that provides fast, accurate and reproducible images to assist physicians in earlier diagnosis and treatment.

Mel Wong, President and CEO of BioAlberta presented the awards with these comments, “We commend Circle Cardiovascular Imaging and Dr. John Lewis for their exceptional achievements in life sciences, Alberta’s life sciences industry is maturing and these award winners exemplify Alberta’s capacity for global impact.”

More than 200 representatives from industry, the investment community, government and innovation support organizations attended the awards gala that was held in partnership with TEC Edmonton, and with generous event sponsors. Read more in this Financial Post article.

Congratulations to John Lewis on receiving BioAlberta’s Scientific Achievement and Innovation Award!

- Perrin Beatty