Revisiting silibinin as a novobiocin-like Hsp90 C-terminal inhibitor: Computational modeling and experimental validation • Tertulias Oncológicas

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.