PU-WS13 is a Grp94 inhibitor, with an EC50 of 0.22 μM. PU-WS13 also slightly suppresses Hsp90α, Hsp90β and Trap-1, with EC50s of 27.3, 41.8 and 7.3 μM, respectively. PU-WS13 (2.5-20 μM) shows no toxicity on two nonmalignant cell lines. PU-WS13 (15 μM) disrupts the circular architecture of HER2 at the plasma membrane of SKBr3 cells mediated through Grp94. PU-WS13 inhibits Grp94, and the inhibition induces apoptosis in and reduce the viability of HER2 overexpressing breast cancer cells