Highlights
- Silibinin is computationally predicted to overlap the novobiocin-binding mode to the C-terminal domain (CTD) of Hsp90.
- Silibinin diminishes the efficiency of Hsp90 CTD binding to its co-chaperone PPID/cyclophilin D in the low millimolar range.
- Silibinin is a novobiocin-like Hsp90 inhibitor binding the CTD to alter Hsp90-co-chaperone-client interactions.
- Silibinin structure avoids unwanted hepatotoxicity, thereby providing a path to develop new Hsp90 inhibitors.
https://www.sciencedirect.com/science/article/pii/S027869151930434X