PU-H71-hydrochloride - HSP 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPU-H71 hydrochlorideCat. No.: HY-11038B分式: CHClINOS分量: 548.83作靶點: HSP作通路: Cell Cycle/DNA Damage; Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 monthBIOLOGICAL ACTIVITY物活性 PU-H71 hydroc

2、hloride種有效的 Hsp90 抑制劑，在 MDA-MB-468 細胞中，對 Hsp90 的 IC50 值為 51nM。IC50 & Target HSP9051 nM (IC50, MDA-MB-468 cells)體外研究 PU-H71 hydrochloride is a potent Hsp90 inhibitor, with an IC50 of 51 nM in MDA-MB-468 cells. PU-H71inhibits the growth of several tumor cells, such as MDA-MB-468, MDA-MB-231 and HCC-18

3、06 cells, withIC50s of 65 8 nM, 140 5 nM and 87 3 nM, respectively, and such inhibition is associated with a G2-Mblock arrest. PU-H71 (10-1000 nM) induces significant apoptosis in triple-negative breast cancers (TNBCs).PU-H71 (0.5, 1 M) also downregulates oncoproteins involved in the invasive potent

4、ial of TNBCs 1. PU-H71(0.5 M) decreases and depletes the BCR signaling kinases. PU-H71 (0.25-10 M) is cytotoxic to CLL cellsbut shows minimal effects on PBMC or resting B cells. In addition, PU-H71 (0-1M) reduces CLL viability viathe induction of mitochondrial apoptosis, and antagonizes the survival

5、 signals from CLL microenvironment at0.5 M 2. PU-H71 (0.05 M) induces apoptosis of MDA-MB-231, BT-474, and MCF7 cells, and suchinduction is enhanced by TNF-. PU-H71 (0.05 M) degradates IKK, and down-regulates the NF-Btranscriptional activity induced by TNF- treatment 3.體內(nèi)研究 PU-H71 (75 mg/kg, i.p.) c

6、auses intratumor accumulation, extends down-regulation of anti-tumor drivingmolecules, completes and retains responses at nontoxic doses in MDA-MB-468 tumor-bearing mice. PU-H71(75 mg/kg 3week, i.p.) suppresses the gowth of tumors, and such an effect is associated with down-regulation of several Hsp

7、90-regulated malignancy driving proteins 1.1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEPROTOCOLKinase Assay 1 Measurements are performed in black 96-well microtiter plates. In short, cell lysates are prepared byrupturing cellular membranes by freezing at -70C and dissolving the cellular extract

8、 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 andphosphatase inhibitors (PU-H71, etc.). Saturation curves are recorded in which fluorescently labeledgeldanamycin (Cy3B-GM) (3 nM) is treated with increasing amounts of cellular lysates. Th

9、e amount of lysatethat results in polarization (mP) readings corresponding to 90%-99% bound ligand is chosen for thecompetition study. Here, each 96-well plate contains 3 nM Cy3B-GM, cellular lysate and tested Hsp90inhibitor in a final volume of 100 L. The plate is left for 24 h on a shaker at 4C, a

10、nd the fluorescencepolarization (FP) values in mP are recorded. EC50 values are determined as the competitor concentrationsat which 50% of the Cy3B-GM is displaced. FP measurements are performed on an Analyst GT microplatereader 1.MCE has not independently confirmed the accuracy of these methods. Th

11、ey are for reference only.Cell Assay 1 The antiproliferative effects of select Hsp90 inhibitors is evaluated using the CellTiter-Glo Luminescent CellViability Assay kit. Briefly, exponentially growing MDA-MB-468, MDA-MB-231, and HCC-1806 cells areseeded into black 96-well microtiter plates and incub

12、ated in medium containing either vehicle control (DMSO)or PU-H71 for the indicated time at 37C. Plates containing 3 replicate wells per assay condition are seededat a density of 8 103 cells for each cell line in 100 L medium. After exposure of cells to the Hsp90inhibitors, plates are equilibrated to

13、 room temperature (20-25C) for approximately 30 min, and 100 LCellTiter-Glo reagent are added to each well. Plates are mixed for 2 min on an orbital shaker and thenincubated for 15 min to 2 h at room temperature. The luminescence signal in each well is measured in anAnalyst GT microplate reader. The

14、 percentage cell growth inhibition is calculated by comparing luminescencereadings obtained from treated versus control cells, accounting for initial cell population (time 0). The IC50 iscalculated as the drug concentration that inhibits cell growth by 50% 1.MCE has not independently confirmed the a

15、ccuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Mice bearing MDA-MB-468 tumors reaching a volume of 100-150 mm3 are treated i.p. using different dosesand 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

16、 at 50 mg/kg 5xqd; group 04 (n = 8) PU-H71 at 75 mg/kg 3 week; group 05 (n = 8) PU-H71 at 75mg/kg on alternate days. Mice bearing HCC-1806 or MDA-MB-231 xenografted tumors receive PU-H71 at 75mg/kg on alternate days. Tumor volume is determined by measurement with Vernier calipers, and tumorvolume is

17、 calculated as the product of its length width2 0.4. Tumor volume is expressed on indicateddays as the median tumor volume SD indicated for groups of mice 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Nat Commun. 2017 Sep 4;8(1):422. The

18、ranostics. 2019 Jan 1;9(2):554-572.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Caldas-Lopes E, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negativebreast cancer mode