受注:045-509-1970 |
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Synonyms | CP127374, NSC-330507, KOS 953 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C31H43N3O8 |
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分子量 | 585.69 | CAS No. | 75747-14-7 | |
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (170.73 mM) | |
Ethanol | 33 mg/mL (56.34 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Tanespimycin (17-AAG, CP127374, NSC-330507, KOS 953) is a potent HSP90 inhibitor with IC50 of 5 nM in a cell-free assay, having a 100-fold higher binding affinity for HSP90 derived from tumour cells than HSP90 from normal cells. Tanespimycin (17-AAG) induces apoptosis, necrosis, autophagy and mitophagy. Phase 3. |
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in vitro | 17-AAG, an analog of geldanamycin, exhibits greater than 100 times higher binding affinity for Hsp90 derived from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells with IC50 values of 5-6 nM. [1] 17-AAG causes the degradation of HER2, HER3, Akt, and both mutant and wild-type androgen receptor (AR), leading to the RB-dependent G1 growth arrest of prostate cancer cells such as LNCaP, LAPC-4, DU-145, and PC-3 with IC50 values of 25-45 nM. [2] In addition to inducing apoptosis of Ba/F3 cells transformed with wild-type BCR-ABL with an IC50 of 5.2 μM, 17-AAG has the ability to induce apoptosis of cells transformed with imatinib mesylate-resistant T315I and E255K BCR-ABL mutants with IC50 values of 2.3 μM and 1.0 μM, respectively, by inducing the degradation of both wild-type BCR-ABL protein and mutants. [3] |
in vivo | 17-AAG displays significantly higher binding affinity for Hsp90 from 3T3-src, B16 or CT26 xenografts in nude mice with IC50 values of 8-35 nM as compared with that from the normal tissues with IC50 values of 200-600 nM. [1] Administration of 17-AAG (~50 mg/kg) causes significant decline in AR, HER2, HER3, and Akt expression in a dose-dependent manner with >50% decline at dose of 50 mg/kg, resulting in the dose-dependent inhibition of androgen-dependent (CWR22) and -independent (CWR22R and CWRSA6) prostate cancer xenografts growth by 67%, 80% and 68% at dose of 50 mg/kg, respectively. [2] |
特徴 | Displays very low toxicity toward normal cells. |
キナーゼアッセイ | Hsp90 binding assays | |
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Purified native Hsp90 protein or cell lysates from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells in lysis buffer (20 mM HEPES, pH 7.3, 1 mM EDTA, 5 mM MgCl2, 100 mM KCl) are incubated with various concentrations of 17-AAG for 30 minutes at 4 °C, and then incubated with biotin-GM linked to BioMag streptavidin magnetic beads for 1 hour at 4 °C. Tubes are placed on a magnetic rack, and the unbound supernatant removed. The magnetic beads are washed three times in lysis buffer and heated for 5 minutes at 95 °C in SDS–PAGE sample buffer. Samples are analysed on SDS protein gels, and western blots done using indicated antibodies. Bands in the western blots are quantified using the Bio-rad Fluor-S MultiImager, and the percentage inhibition of binding of Hsp90 to the biotin-GM is calculated. The IC50 reported is the concentration of 17-AAG needed to cause half-maximal inhibition of binding. | ||
細胞アッセイ | 細胞株 | BT474, SKBR3, N87, SKOV3, MCF7, MDA468, Hs578T, Hs578Bst, A549, HT29, U87, SKMG3, HT1080, RPTEC, NDF, HMVEC, HMEC, HUVEC, and PBMC cells |
濃度 | Dissolved in DMSO, final concentrations ~10 μM | |
反応時間 | 5 days | |
実験の流れ | Cells are seeded in 96-well plates at 2,000 cells per well in a final culture volume of 100 μL for 24 hours before the addition of increasing concentrations of 17-AAG that is incubated for 5 days. Viable cell number is determined using the Celltiter 96 AQueous Nonradioactive Cell Proliferation Assay. The value of the background absorbance at 490 nm (A490) of wells not containing cells is subtracted. Percentage of viable cells = (A490 of 17-AAG treated sample/A490 untreated cells) × 100. The IC50 is defined as the concentration that gave rise to 50% viable cell number. | |
動物実験 | 動物モデル | Male nu/nu athymic mice inoculated s.c. with androgen-dependent CWR22 xenograft, and female nu/nu athymic mice inoculated s.c. with androgen-independent xenografts CWR22R and CWRSA6 |
投薬量 | ~50 mg/kg | |
投与方法 | Injection i.p. |
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Data from [Data independently produced by Mol Cancer, 2014, 13, 150]
Data from [Data independently produced by Oncotarget, 2014, 5, 4269-82]
Data from [Mol Cell Biol, 2013, 33(12), 2375-87]
The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer [ Theranostics, 2024, 14(6):2442-2463] | PubMed: 38646654 |
Caspase-2 protects against ferroptotic cell death [ Cell Death Dis, 2024, 15(3):182] | PubMed: 38429264 |
Amyloid aggregates induced by the p53-R280T mutation lead to loss of p53 function in nasopharyngeal carcinoma [ Cell Death Dis, 2024, 15(1):35] | PubMed: 38212344 |
RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway [ Oncogenesis, 2024, 13(1):12] | PubMed: 38453884 |
Up-regulation of HSP90α in HDM-induced asthma causes pyroptosis of airway epithelial cells by activating the cGAS-STING-ER stress pathway [ Int Immunopharmacol, 2024, 131:111917] | PubMed: 38527402 |
HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer [ Sci Adv, 2024, 10(8):eadk3663] | PubMed: 38394204 |
Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease [ Signal Transduct Target Ther, 2023, 8(1):229] | PubMed: 37321990 |
The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma [ Nat Commun, 2023, 14(1):1516] | PubMed: 36934113 |
FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways [ Mol Cell, 2023, 83(15):2810-2828.e6] | PubMed: 37541219 |
Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis [ J Exp Clin Cancer Res, 2023, 42(1):203] | PubMed: 37563605 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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