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Chemical Structure| 873436-91-0 同义名 : Pu-h 71; NSC 750424; PU-H71
CAS号 : 873436-91-0
货号 : A241620
分子式 : C18H21IN6O2S
纯度 : 99%+
分子量 : 512.37
MDL号 : MFCD18251588
存储条件：

Pure form Keep in dark place, inert atmosphere, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Heat shock protein 90 (Hsp90) is a molecular chaperone protein that stabilizes client oncogenic proteins in breast cancer cells. PU-H71 is a novel Hsp90 inhibitor with an IC50 value of 51nM. The treatment with PU-H71 at a dosage of 1µM resulted in significant cell death in triple-negative breast cancer (TNBC) cell lines MDA-MB-468 (80%), MDA-MB-231 (65%), and HCC-1806 (80%). The inhibition of Hsp90 by PU-H71 (10–1000nM) induced a concentration-dependent inactivation or degradation of tumor driving molecules, including epidermal growth factor receptor, insulin-like growth factor receptor, HER3, and c-Kit. PU-H71 (10–1000nM) also downregulated the proteins related to G2-M progression, such as cyclin-dependent kinase 1 and checkpoint kinase 1. The treatment of MDA-MB-468 cells with 0.25, 0.5, and 1μM PU-H71 for 24 h increased the percentage of cells in G2-M phase to 30%, 44%, and 69%, respectively. PU-H71 at 250–1000nM induced apoptosis in TNBC cells by inactivating and downregulating Bcl-xL and Akt. The treatment of MDA-MB-231 cells with 0.5 and 1μM PU-H71 for 24 h reduced the NF-κB activity by 84% and 90%, respectively. In the MDA-MB-231 xenograft mouse model, PU-H71 (75 mg/kg on an alternate day schedule) completely inhibited tumor growth after 37 days of treatment. In the fast growing HCC-1806 tumors, six doses of PU-H71 (75 mg/kg on an alternate day schedule) over a 12 days resulted in an 87% regression in tumor volume.
作用机制 PU-H71 is a potent inhibitor of Hsp90 both in vitro and in vivo. When Hsp90 is inactivated, many TNBC oncoproteins that form a complex with PU-H71-bound Hsp90 become destabilized and subsequently degraded.
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
H69AR cells Function assay 96 h Inhibition of HSP90-mediated antiapoptotic activity in human H69AR cells assessed as induction of cell growth arrest at 10 after 96 hrs by propidium iodide staining-based flow cytometry 17603540
MCF7 cells Function assay 24 h Inhibition of Hsp90 in human MCF7 cells assessed as Her2 level after 24 hrs by Western blot, IC50=0.06 μM 18571929
MDA-MB-468 cells Function assay Inhibitory activity against Hsp90 in human breast cancer MDA-MB-468 cell line, EC50=0.0102 μM 16392823
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.95mL

0.39mL

0.20mL

9.76mL

1.95mL

0.98mL

19.52mL

3.90mL

1.95mL
参考文献

[1]Gallerne C, Prola A, et al. Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2. Biochim Biophys Acta. 2013 Jun;1833(6):1356-66.

[2]Caldas-Lopes E, Cerchietti L, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8368-73.