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受注：045-509-1970 |
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化学情報
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Synonyms | NSC 707545,BMS 826476 HCl,KOS 1022 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C32H48N4O8•HCl |
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| 分子量 | 653.21 | CAS No. | 467214-21-7 | |
| Solubility (25°C)* | 体外 | DMSO | 131 mg/mL (200.54 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl is a potent HSP90 inhibitor with IC50 of 62 nM in a cell-free assay. Phase 2. |
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| in vitro | 17-DMAG displays ~2 times potency against human Hsp90 than 17-AAG, with IC50 of 62 nM versus 119 nM. In SKBR3 and SKOV3 cells which over-express Hsp90 client protein Her2, 17-DMAG causes down-regulation of Her2 with EC50 of 8 nM and 46 nM, respectively, as well as induction of Hsp70 with EC50 of 4 nM and 14 nM, respectively, leading to significant cytotoxicity with GI50 of 29 nM and 32 nM, respectively, consistent with Hsp90 inhibition. [1] 17-DMAG in combination with vorinostat synergistically induces apoptosis of the cultured MCL cells as well as primary MCL cells, more potently than either agent alone, by markedly attenuating the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and Akt. [3] In contrast to 17-AAG which is only active for IKKβ in chronic lymphocytic leukemia (CLL) cells, 17-DMAG treatment effectively leads to depletion of the Hsp90 client protein, resulting in diminished NF-κB p50/p65 DNA binding, decreased NF-κB target gene transcription, and caspase-dependent apoptosis. By targeting the NF-κB family, 17-DMAG selectively mediates dose- and time-dependent cytotoxicity against CLL cells, but not normal T cells or NK cells important for immune surveillance. [5] |
| in vivo | 17-DMAG treatment at 5 mg/kg or 25 mg/kg thrice per week significantly reduces tumor growth of TMK-1 xenografts, by significantly reducing vessel area and numbers of proliferating tumor cells in sections. [2] Consistent the inhibition of FAK signaling in vivo, 17-DMAG treatment at 25 mg/kg three times a week significantly suppresses tumor growth, and metastasis of ME180 and SiHa xenografts in mice. [4] Administration of 17-DMAG at 10 mg/kg for 16 days significantly decreases the white blood cell count and prolongs the survival in a TCL1-SCID transplant mouse model. [5] |
| 特徴 | A synthetic derivative Geldanamycin, with lower hepatotoxicity than parent antibiotic & higher potency and bioavailability than the similar derivative 17-AAG. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Fluorescence polarization (FP)-based competition binding assay | |
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| This assay utilizes a boron difluoride dipyrromethene (BODIPY) labeled geldanamycin analogue (BODIPY-AG) as a probe and measured fluorescence polarization upon binding of the probe to a protein. Native human Hsp90 protein (α + β isoforms) is isolated from HeLa cells. BODIPY-AG solution is freshly prepared in FP assay buffer (20 mM HEPES-KOH, pH 7.3, 1.0 mM EDTA, 100 mM KCl, 5.0 mM MgCl2, 0.01% NP-40, 0.1 mg/mL fresh bovine γ-globulin (BGG), 1.0 mM fresh DTT, and protease inhibitor from stock solution in DMSO. Competition curves are obtained by mixing 10 μL each of a solution containing BODIPY-AG and Hsp90, and a serial dilution of 17-DMAG freshly prepared in FP assay buffer from stock solution in DMSO. Final concentrations are 10 nM BODIPY-AG, 40 or 60 nM Hsp90, varying concentration of 17-DMAG (0.10 nM-10 μM), and ≤0.25% DMSO in a 384-well microplate. After 3 hours incubation at 30 °C, fluorescence anisotropy (γEx = 485 nm, γEm = 535 nm) is measured on an EnVision 2100 multilabel plate reader. IC50 value of 17-DMAG is obtained from the competition curves. | ||
| 細胞アッセイ | 細胞株 | Chronic lymphocytic leukemia (CLL) |
| 濃度 | Dissolved in DMSO, final concentrations ~1 μM | |
| 反応時間 | 24, or 48 hours | |
| 実験の流れ | Cells are exposed to various concentrations of 17-DMAG for 24, or 48 hours. For the assessment of cytotoxicity, MTT reagent is then added, and plates are incubated for an additional 24 hours before spectrophotometric measurement. Apoptosis is determined by staining with annexin V-fluorescein isothiocyanate and propidium iodide (PI). |
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| 動物実験 | 動物モデル | SCID mice engrafted with TCL1 leukemia cells |
| 投薬量 | 10 mg/kg | |
| 投与方法 | Intraperitoneal injection 5 times per week | |
参考
カスタマーフィードバック
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Data from [Data independently produced by Mol Oncol, 2013, 7(6), 1093-102]
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Data from [Data independently produced by J Thorac Oncol, 2012, 7(7), 1078-85]
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Data from [Data independently produced by J Thorac Oncol, 2012, 7(7), 1078-85]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Stress response silencing by an E3 ligase mutated in neurodegeneration [ Nature, 2024, 626(8000):874-880] | PubMed: 38297121 |
| Cytokine-Induced Killer Cells in Combination with Heat Shock Protein 90 Inhibitors Functioning via the Fas/FasL Axis Provides Rationale for a Potential Clinical Benefit in Burkitt's lymphoma [ Int J Mol Sci, 2023, 24(15)12476] | PubMed: 37569852 |
| Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses [ Virus Res, 2023, 329:199103] | PubMed: 36963723 |
| Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis [ J Biol Chem, 2023, 299(5):104668] | PubMed: 37011862 |
| Alvespimycin Inhibits Heat Shock Protein 90 and Overcomes Imatinib Resistance in Chronic Myeloid Leukemia Cell Lines [ Molecules, 2023, 28(3)1210] | PubMed: 36770876 |
| Local Elimination of Senescent Cells Promotes Bone Defect Repair during Aging [ ACS Appl Mater Interfaces, 2022, 10.1021/acsami.1c22138] | PubMed: 35014784 |
| Inflammation accelerates BCR-ABL1+ B-ALL development through upregulation of AID [ Blood Adv, 2022, 6(13):4060-4072] | PubMed: 35816360 |
| Hsp90 Regulates GCRV-II Proliferation by Interacting with VP35 as Its Receptor and Chaperone [ J Virol, 2022, 96(19):e0117522] | PubMed: 36102647 |
| Hsp90 Regulates GCRV-II Proliferation by Interacting with VP35 as Its Receptor and Chaperone [ Journal of Virology, 2022, Vol. 96, No. 19] | PubMed: None |
| Therapeutic Response Monitoring with 89Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer Models [ Pharmaceutics, 2022, 14(7)1338] | PubMed: 35890234 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。