BIIB021 is an orally available, synthetic small-molecule Hsp90 inhibitor. It binds in the ATP-binding pocket of Hsp90 (Ki = 1.7 ± 0.4 nM) and induces HER-2 degradation with an EC50 of 38 ± 10 nM in MCF-7 cells. It ncreases expression of the heat shock proteins Hsp90α and Hsp70, but has no effect on expression of the nonclient protein phosphatidylinositol 3-kinase p85 subunit. BIIB021 inhibits the proliferation of N87, MCF-7, and BT474 tumor cells with IC50 values of 0.06, 0.31, and 0.14 µM, respectively. It has significant antitumor activity in N87 stomach, BT474 breast, CWR22 prostate, U87 glioblastoma, SKOV3 ovarian, and Panc-1 pancreatic tumor xenograft models.