In vitro anti-MM activity of hsp90 inhibitors. (A) In vitro anti-MM activity of geldanamycin against both drug-sensitive and drug-resistant MM cell lines, including the Dex-resistant MM-1R and the doxorubicin-resistant RPMI-8226/Dox40 cells. (B) Comparative in vitro activity of geldanamycin and its analogs against MM-1S myeloma cells. (C) In vitro activity of the geldanamycin analog 17-AAG (NSC 330507) against primary MM tumor cells isolated from patients resistant to conventional or investigational therapies (including conventional or high-dose chemotherapy, thalidomide, IMiDs, or the proteasome inhibitor PS-341). For each sample, red bars represent the percent survival (mean ± SD) of drug-treated cells; blue bars, the survival of their respective controls. (D) Dose-response matrix of human MM cell lines (as well as cells from other B-cell malignancies, such as IM-9 and ARH-77) to 17-AAG in vitro (0-5 μM for 72 hours). The survival of 17-AAG-treated cells (expressed as percent of the vehicle-treated control) is visualized in color format according to their values on a linear scale (0-100%).