Figure 2
Pharmacokinetic/pharmacodynamic analysis of NVP-AUY922 in BT-474 tumor-bearing nude mice. A pharmacokinetic profile of NVP-AUY922 in BT-474 tumor xenografts, plasma, and organs (liver, heart, lung, and muscle) after administration of a single dose is shown. Female athymic mice bearing subcutaneous xenotransplants of the human ductal breast carcinoma BT-474 of approximately 250 mm3 received a single dose of 30 mg/kg of NVP-AUY922 (intravenous) at 0 hours. (a) NVP-AUY922 concentrations were determined by HPLC/MS-MS analysis using an internal standard method. The limits of quantification for plasma and tissues were set to 4.0 ng/mL and 10 ng/g, respectively. Bars represent standard error of the mean (n = 4). (b) Pharmacodynamic analysis in BT-474 xenografts following a single NVP-AUY922 dose. The amount of p23 associated with HSP90 was determined by immunoprecipitating HSP90 followed by immunoblotting for p23. The levels of AKT, phosphorylated AKT and β-tubulin were determined by immunoblotting. HPLC/MS-MS, high-pressure liquid chromatography/tandem mass spectrometry; HSP90, heat shock protein 90; IP, immunoprecipitation.