NVP-AUY922, Free Base (AUY922, Luminespib, VER-52296, CAS 747412-49-3), >99%

LC Laboratories' Product Number N-5300 - NVP-AUY922, Free Base (AUY922, Luminespib, VER-52296, CAS 747412-49-3), >99% - for research use only. NVP-AUY922 potently inhibited HSP90 with IC50 values of 7.8 nM and 21 nM, and Ki values of 9 nM and 8.2 nM for HSP90α and HSP90β, respectively. NVP-AUY922 showed a very high binding affinity to HSP90β with a Kd of 1.7 nM. NVP-AUY922 inhibited the proliferation of human tumor cells in vitro with GI50 values of approximately 2 to 40 nM, inducing G1-G2 arrest and apoptosis. Human endothelial cells were very sensitive to NVP-AUY922 with GI50s of 2.5-3.9 nM. NVP-AUY922 also exhibited potent antitumor efficacy in human tumor xenografts including BT474 breast, A2780 ovarian, U87MG glioblastoma, PC3 prostate, and WM266.4 melanoma. NVP-AUY922 showed impressive synergistic inhibitory effect with histone deacetylase inhibitors, melphalan, doxorubicin, NVP-LBH589 (Panobinostat), and suberoylanilide hydroxamic acid (SAHA, Vorinostat) on the growth of multiple myeloma cell lines and primary myeloma cells. NVP-AUY922 potently inhibited the proliferation of human breast cancer cell lines with GI50 values in the range of 3 to 126 nM. NVP-AUY922 induced proliferative inhibition concordant with HSP70 upregulation and client protein depletion. Significant growth inhibition of BT-474 tumor and good tolerability were observed in athymic mice when NVP-AUY922 was administered once per week. Therapeutic effects were also concurrent with changes in pharmacodynamic markers, including HSP90-p23 dissociation, decreases in ERBB2 and P-AKT, and increased HSP70 protein levels. Prostate-specific antigen (PSA) may serve as a sensitive biomarker of Hsp90 inhibition. (89)Zr-bevacizumab PET was concordant with the antiangiogenic response and direct antitumor effects after NVP-AUY922 treatment. It provided a noninvasive tool to monitor tumor VEGF levels. NVP-AUY922 effectively reduces human epidermal growth factor receptor-2 (HER2), which can be monitored with (89)Zr-trastuzumab PET in vivo non-invasively. It might serve as an early biomarker for HSP90 inhibition in HER2 positive metastatic breast cancer patients. Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 enhanced radiosensitivity in four tumor cell lines tested (A549, GaMG, HT 1080, and SNB19).

• Supplier: LC Laboratories
• Product #: N-5300
• Sku #: N-5300_100mg