Oxidative DNA damage, if unrepaired, can lead to cancer, inflammation, and neurodegenerative diseases. Cancer cells often upregulate their repair machinery to survive, making inhibition of DNA repair enzymes an attractive therapeutic strategy to target cancer and inflammation. Conversely, enhanced repair of oxidative DNA damage is beneficial in neurodegenerative diseases. Our lab focuses on discovering drugs targeting DNA glycosylases, a family of 11 DNA repair enzymes. We have developed inhibitors and activators for OGG1, progressing towards clinical trials. This project aims to target 2 other DNA glycosylases using BioSolveIT tools for ultra-large high-throughput virtual screening (uHTVS) and structure-based design (SBDD) to identify and subsequently improve hits identified from on-demand and focused chemical libraries.
Evert intends to achieve the following milestones:
- Getting acquainted with the software
- Potential ligands through uHTVS identified
- SAR exploration of uHTVS hits initiated