| References: |
PU-WS13 is cell-permeable 6-amino-purine based compound that selectively binds to Grp94 and inhibits its activity (EC50 = 220 nM). Exhibits much reduced activity towards other paralogs (EC50 = 27 µM, 42 µM, and 7.3 µM for Hsp90α, Hsp90β and Trap-1, respectively). Disrupts HER2 architecture in plasma membrane and reduces the viability of HER2 over-expressing SKBr3 breast cancer cells in a dose-dependent manner. Blocks their proliferation at the sub-G1 phase and induces apoptosis. Causes rapid inactivation of Raf-1-MAP kinase signaling at the membrane, but not in the cytosol indicating the requirement of Grp94 for HER2 architecture. Does not appear to be toxic to non-malignant cells. Unlike pan-Hsp90 and the cytosolic Hsp90 inhibitors, it does not activate any feedback heat-shock response. |
