Identification of a new scaffold for hsp90 C-terminal inhibition

Inhibition of HSP90 C-terminal function is an advantageous therapeutic paradigm for the treatment of Cancer. Currently, the majority of HSP90 C-terminal inhibitors are derived from novobiocin, a natural product traditionally used as an Antibiotic. Assisted by molecular docking studies, a scaffold containing a biphenyl moiety in lieu of the coumarin ring system found in novobiocin was identified for development of new HSP90 C-terminal inhibitors. Initial structure-activity studies led to derivatives that manifest good antiproliferative activity against two breast Cancer cell lines through HSP90 inhibition. This platform serves as a scaffold upon which new HSP90 C-terminal inhibitors can be readily assembled for further investigation.

Heat shock protein 90; Hsp90 C-terminal inhibitors; biphenyl; breast cancer; novobiocin.