Tanespimycin-17-AAG-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETanespimycinCat. No.: HY-10211CAS No.: 75747-14-7Synonyms: 17-AAG; NSC 330507; CP 127374分式: CHNO分量: 585.69作靶點: HSP; Autophagy; Mitophagy作通路: Cell Cycle/DNA Damage; Metabolic Enzyme/Protease;Autophagy儲存式: 4C, protect from light*

2、In solvent : -80C, 6 months; -20C, 1 month (protect fromlight)溶解性數(shù)據(jù)體外實驗 DMSO : 55 mg/mL (93.91 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.7074 mL 8.5369 mL 17.0739 mL5 mM 0.3415 mL 1.7074 mL 3.4148 mL10 mM 0.1707 mL 0.85

3、37 mL 1.7074 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Tanespimycin (17-AAG)有效的 HSP90 抑制劑，IC50 為 5 nM，對腫瘤細胞 HSP90 的親和性正常細胞100 倍。IC50 & Target HSP90 Autophagy Mitophagy1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE5 nM (IC50)體外研究 Tanespimycin causes the degradation of HE

4、R2, Akt, and both mutant and wild-type AR and theretinoblastoma-dependent G1 growth arrest of prostate cancer cells. Tanespimycin inhibits prostate cancercell lines with IC50s ranged from 25-45 nM (LNCaP, 25 nM; LAPC-4, 40 nM; DU-145, 45 nM; and PC-3, 25nM) 1. Tanespimycin (0.1-1 M) induces a nearly

5、 complete loss of ErbB2 on ErbB2-overexpressing breastcancer cells 2. Tanespimycin inhibits cell growth and induces G2/M cell cycle arrest and apoptosis in CCAcells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleavedPARP 3.體內(nèi)研究 Tanespimycin (25-200 mg

6、/kg, i.p.) causes a dose-dependent decline in AR, HER2, and Akt expression inprostate cancer xenografts. Tanespimycin treatment at doses sufficient to induce AR, HER2, and Aktdegradation results in the dose-dependent inhibition of androgen-dependent and -independent prostatecancer xenograft growth w

7、ithout toxicity 1. Tanespimycin (60 mg/kg) with Rapamycin (30 mg/kg) inhibitsA549 and MDA-MB-231 tumor growth and effects tumor cures in MDA-MB-231 tumor-bearing animals by tailvein injection 4.PROTOCOLCell Assay 1 For the Alamar Blue proliferation assay, 2-4103 cells are plated in 96-well plates. L

8、ater (48 h), cells aretreated with Tanespimycin for 96 h or 0.01% DMSO as control. On day 4, Alamar Blue viability assay isperformed as described elsewhere. IC50 and IC90s are calculated as the doses of Tanespimycin required toinhibit cell growth by 50 and 90%, respectively. Cell cycle distribution

9、is assayed as described previously witha Becton Dickinson fluorescence-activated cell sorter and analyzed by the Cell Cycle Multicycle system.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Tanespimycin is dissolved in an EPL vehicle. To aid in t

10、he identification of an optimal dose and schedule,Administration 1 nontumor bearing mice are treated by i.p. injection with 25-200 mg/kg of Tanespimycin 5 days/week for 3weeks or by the EPL vehicle alone. Serum samples are taken from each group, and equal volumes arepooled on days 5, 10, and 15 of t

11、reatment for serum chemistry and liver function analysis. At sacrifice,plasma samples are collected for complete blood count. A gross necropsy is performed on all of the mice,and a complete necropsy, including histopathology, is performed on 1 animal/group.MCE has not independently confirmed the acc

12、uracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Theranostics. 2018 Feb 15;8(7):2044-2060. Cell Death Dis. 2018 Feb 7;9(2):165. J Exp Clin Cancer Res. 2018 Mar 27;37(1):70. Mol Cancer Ther. 2016 Sep;15(9):2107-18. Front Mol Neurosci. 2018 Nov 6;11:401.See more customer validations on

13、HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Solit DB, et al. 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits thegrowth of prostate cancer xenografts.Clin Cancer Res, 2002, 8(5), 986-993.2. Raja,

14、Srikumar M., et al. 17-AAG induces enhanced ubiquitinylation and lysosomal pathway-dependent ErbB2 degradation andcytotoxicity in ErbB2-overexpressing breast cancer cells. Cancer Biology & Therapy (2008), 7(10), 1633. Zhang J, et al. The heat shock protein 90 inhibitor 17-AAG suppresses growth and i

15、nduces apoptosis in human cholangiocarcinomacells.Clin Exp Med. 2012 Sep 7.4. Newman B, et al. HSP90 Inhibitor 17-AAG Selectively Eradicates Lymphoma Stem Cells.Cancer Res. 2012 Sep 1;72(17):4551-61. Epub2012 Jun 29.5. Kamal A, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature. 20