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- Arzneimitteldesign (1)
- Aurora-A (1)
- Aurora-A-MYCN-Komplex (1)
- MYCN (1)
- MYCNv (1)
- PROTAC (1)
- Protein-Protein-Wechselwirkung (1)
- Proteolysis-Targeting-Chimera (1)
- Vernetzung <Chemie> (1)
- Wirkstoffdesign (1)
- neuroblastoma cell (1)
- proteasome system (1)
Formation of the Aurora-A–MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A–MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A–MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.