NVP-AUY922, Free Base **

产品名称：NVP-AUY922, Free Base
产品货号：LC  N-5300     
产品规格：100 MG
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.  Eccles, S.A., et al.  "NVP-AUY922:  a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis."  Cancer Res. 68:  2850-2860 (2008).
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.  Kaiser, M., et al.  "Synergistic action of the novel HSP90 inhibitor NVP-AUY922 with histone deacetylase inhibitors, melphalan, or doxorubicin in multiple myeloma."  Eur. J. Haematol. 84:  337-344 (2010).
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.  Jensen, M.R., et al.  "NVP-AUY922:  a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models."  Breast Cancer Res. 10:  R33 (2008).
Prostate-specific antigen (PSA) may serve as a sensitive biomarker of Hsp90 inhibition.  Oikonomopoulou, K., et al.  "Evaluation of prostate-specific antigen as a novel biomarker of Hsp90 inhibition."  Clin. Biochem. 42:  1705-1712 (2009).
89Zr-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.  Nagengast, W.B., et al.  "89Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922."  J. Nucl. Med. 51:  761-767 (2010).
NVP-AUY922 effectively reduces human epidermal growth factor receptor-2 (HER2), which can be monitored with 89Zr-trastuzumab PET in vivo non-invasively.  It might serve as an early biomarker for HSP90 inhibition in HER2 positive metastatic breast cancer patients.  Oude Munnink, T.H., et al.  "89Zr-trastuzumab PET visualises HER2 downregulation by the HSP90 inhibitor NVP-AUY922 in a human tumour xenograft."  Eur. J. Cancer 46:  678-684 (2010).
Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 enhanced radiosensitivity in four tumor cell lines tested (A549, GaMG, HT 1080, and SNB19).  Stingl, L., et al.  "Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell-cycle impairment, increased DNA damage and repair protraction."  Br. J. Cancer 102:  1578-1591 (2010).
Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO at 100 mg/mL; soluble in ethanol at 100 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 25-50 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility.  Disposal:  A

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