Figure 1. Structure–activity relationships between novobiocin, KU-32 and KU-174 that diverge client protein degradation from induction of Hsp70.

(a) Structure of analogues and theoretical representation of concentrations affecting client protein degradation (dotted lines) and chaperone induction (solid lines) for novobiocin (black), KU-32 (blue) and KU-174 (red). (b) KU-32 induces Hsp70 expression but shows limited degradation of the Hsp90 client protein Akt. (c) KU-174 promotes Akt degradation but does not increase Hsp70 levels. MCF7 cells were treated with the indicated concentration of inhibitors for 24 h and immunoblot analysis was performed. (d) Band intensities were normalized to β-actin and expressed as a percentage of the control (n = 3).