PU-H71 (Synonyms: PU-H 71; PU H71) |
Catalog No.GC15143
One-Click Copy Product Info
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Hsp90 inhibitor,potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 873436-91-0
Sample solution is provided at 25 µL, 10mM.
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PU-H71 is a potent and selective purine scaffold inhibitor of Hsp90 (Heat shock protein 90) [1].
Hsp90 is a molecular chaperone, it takes participate in a variety of cellular processes through promoting the folding, assembly and transport of its client proteins. Hsp90 is found to overexpress in many kinds of cancer cells. It serves as a protector of the oncoproteins which are also the client of Hsp90. Therefore, Hsp90 is thought to be an attractive target of the cancer therapy. The Hsp90 inhibitors found so far can be categorized into several classes according to the mechanisms. Among these, the inhibitors which bind to Hsp90 within its N-terminal ATP binding site are most explored. PU-H71 is one of this sort of inhibitors [2, 3 and 4].
As an inhibitor of Hsp90, PU-H71 is found to induce the degradation of Her2 through blocking the interaction of Hsp90 and Her2. In SKBr3 breast cancer cells, PU-H71 induced Her2 degradation with EC50 value of 50 nM. In MDA-MB-468 breast cancer cells, PU-H71 showed antimitotic efficacy with IC50 value of 70 nM. PU-H71 affected the growth of a serious of cancer cells with IC50 values of 50 nM, 58 nM and 100 to 300 nM in SKBr3, MDA-MB-468 and human myeloma cells (such as NCI-H929, U266 and MM-IR). Besides that, PU-H71 is found to cause cell cycle arrest through reducing the levels of CDK1 and Chk1 which are essential for the G2-M progression [1, 2 and 3].
PU-H71 administration significantly reduced the tumor size in mice injected with A673 tumor cells. In mice bearing MDA-MB-468 tumor xenografts, PU-H71 administration at dose of 75 mg/kg, 3 week remarkably inhibited tumor growth and proliferation by 96% and 60%, respectively. Moreover, PU-H71 is found to down-regulate some Hsp90-regulated malignancy driving proteins when treated in the animal, such as Raf-1, HER3, EGFR and PARP [5, 6].
References:
[1]. He H, Zatorska D, Kim J, et al. Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. Journal of medicinal chemistry, 2006, 49(1): 381-390.
[2]. Usmani S Z, Bona R D, Chiosis G, et al. The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1. J Hematol Oncol, 2010, 3(1): 40.
[3]. Caldas-Lopes E, Cerchietti L, Ahn J H, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proceedings of the National Academy of Sciences, 2009, 106(20): 8368-8373.
[4]. Liu M, Wang J, Wu X, et al. HPLC method development, validation and impurity characterization for an antitumor Hsp90 inhibitor—PU-H71 (NSC 750424). Journal of pharmaceutical and biomedical analysis, 2014, 89: 34-41.
[5]. Ambati S R, Lopes E C, Kosugi K, et al. Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma. Molecular oncology, 2014, 8(2): 323-336.
[6]. Gallerne C, Prola A, Lemaire C. 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. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2013, 1833(6): 1356-1366.
Kinase experiment: | Measurements are performed in black 96-well microtiter plates. In short, cell lysates are prepared by rupturing cellular membranes by freezing at -70°C and dissolving the cellular extract in HFB [20 mM Hepes (K), pH 7.3, 50 mM KCl, 5 mM MgCl2, 20 mM Na2MoO4, 0.01% Nonidet P-40] with added protease and phosphatase inhibitors (PU-H71, etc.). Saturation curves are recorded in which fluorescently labeled geldanamycin (Cy3B-GM) (3 nM) is treated with increasing amounts of cellular lysates. The amount of lysate that results in polarization (mP) readings corresponding to 90%-99% bound ligand is chosen for the competition study. Here, each 96-well plate contains 3 nM Cy3B-GM, cellular lysate and tested Hsp90 inhibitor in a final volume of 100 μL. The plate is left for 24 h on a shaker at 4°C, and the fluorescence polarization (FP) values in mP are recorded. EC50 values are determined as the competitor concentrations at which 50% of the Cy3B-GM is displaced. FP measurements are performed on an Analyst GT microplate reader[1]. |
Cell experiment: | The antiproliferative effects of select Hsp90 inhibitors is evaluated using the CellTiter-Glo Luminescent Cell Viability Assay kit. Briefly, exponentially growing MDA-MB-468, MDA-MB-231, and HCC-1806 cells are seeded into black 96-well microtiter plates and incubated in medium containing either vehicle control (DMSO) or PU-H71 for the indicated time at 37°C. Plates containing 3 replicate wells per assay condition are seeded at a density of 8 × 103 cells for each cell line in 100 μL medium. After exposure of cells to the Hsp90 inhibitors, plates are equilibrated to room temperature (20-25°C) for approximately 30 min, and 100 μL CellTiter-Glo reagent are added to each well. Plates are mixed for 2 min on an orbital shaker and then incubated for 15 min to 2 h at room temperature. The luminescence signal in each well is measured in an Analyst GT microplate reader. The percentage cell growth inhibition is calculated by comparing luminescence readings obtained from treated versus control cells, accounting for initial cell population (time 0). The IC50 is calculated as the drug concentration that inhibits cell growth by 50%[1]. |
Animal experiment: | Mice[1]Mice bearing MDA-MB-468 tumors reaching a volume of 100-150 mm3 are treated i.p. using different doses and schedules: Group 01 (n = 8) PBS; group 02 (n = 8) PU-H71 at 50 mg/kg on alternate days; group 03 (n = 8) PU-H71 at 50 mg/kg 5xqd; group 04 (n = 8) PU-H71 at 75 mg/kg 3 week; group 05 (n = 8) PU-H71 at 75 mg/kg on alternate days. Mice bearing HCC-1806 or MDA-MB-231 xenografted tumors receive PU-H71 at 75 mg/kg on alternate days. Tumor volume is determined by measurement with Vernier calipers, and tumor volume is calculated as the product of its length × width2 × 0.4. Tumor volume is expressed on indicated days as the median tumor volume ± SD indicated for groups of mice[1]. |
References: [1]. Caldas-Lopes E, 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. | |
| Cas No. | 873436-91-0 | SDF | |
| Synonyms | PU-H 71; PU H71 | ||
| Chemical Name | 8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine | ||
| Canonical SMILES | CC(C)NCCCN1C2=C(C(=NC=N2)N)N=C1SC3=C(C=C4C(=C3)OCO4)I | ||
| Formula | C18H21IN6O2S | M.Wt | 512.37 |
| Solubility | Soluble in DMSO > 10 mM | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9517 mL | 9.7586 mL | 19.5171 mL |
| 5 mM | 390.3 μL | 1.9517 mL | 3.9034 mL |
| 10 mM | 195.2 μL | 975.9 μL | 1.9517 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)