Fig. 1.

Ganetespib activity in hormone receptor-positive breast cancer cells in vitro and in vivo. a T47D cells were treated with increasing concentrations of ganetespib for 24 h. The levels of PR B, PR A, ERα and HSP70 were determined by immunoblotting. GAPDH was included as a loading control. b T47D cells were exposed to graded concentrations of ganetespib for 6 and 24 h as indicated. Cell lysates were immunoblotted using antibodies against PR B, PR A, ERα, HSP70, phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK), phosphorylated PDK1 (p-PDK1) and GAPDH as shown. c Mice bearing established MCF-7 xenografts (n = 8/group) were i.v. dosed with 100 mg/kg ganetespib once weekly over a 3 week cycle. % T/C values are indicated to the right of each growth curve and the error bars are the SEM. Ganetespib treatment significantly suppressed tumor growth (*, p < 0.05). d Pharmacodynamic analysis. Mice bearing MCF-7 tumors (n = 3/group) were treated with vehicle or a single bolus injection of ganetespib at 125 mg/kg for 24, 72 and 96 h. Tumors were resected and the levels of ERα, Cdc2 and GAPDH determined by immunoblotting