17-DMAG (Alvespimycin) HCl
(Synonyms: 阿螺旋霉素盐酸盐; 17-DMAG hydrochloride; KOS-1022; BMS 826476) 目录号 : GC13044
17-DMAG (Alvespimycin) HCl是一种有效的Hsp90的抑制剂，其IC50值为62nM。
Cas No.:467214-21-7
Sample solution is provided at 25 µL, 10mM.
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17-DMAG (Alvespimycin) HCl is an effective inhibitor of Hsp90, with an IC50 value of 62nM [1]. 17-DMAG (Alvespimycin) HCl binds to the ATP binding motif of Hsp90 and inhibits its protein folding protection activity, resulting in the misfolding and degradation of the target proteins of Hsp90 (such as EGFR, AKT, mutant p53 and IKK) [2]. 17-DMAG (Alvespimycin) HCl has anti-tumor effects and can be used in cancer research such as lung cancer, liver cancer, and colon cancer [3-4].
In vitro, 17-DMAG (Alvespimycin) HCl (50-500nM; 24 or 48h) treatment significantly and dose- and time-dependently led to depletion of the target protein IKK in chronic lymphocytic leukemia (CLL) cells and cysteine aspartate-dependent apoptosis, reducing the binding of NF-κB p50/p65 DNA and the transcription of NF-κB target genes [5]. 17-DMAG (Alvespimycin) HCl (0-1000nM; 24h) treatment inhibits the proliferation of osteosarcoma cells in a dose-dependent manner and inhibits the activation of MET protein and the cell cycle progression [6].
In vivo, 17-DMAG (Alvespimycin) HCl (10mg/kg/day; 5 times per week for 16 days; i.p.) treatment significantly reduces the number of white blood cells in the blood of TCL1-SCID transgenic mouse models and prolongs survival [5]. The treatment with 17-DMAG (Alvespimycin) HCl (5mg/kg/day; 3 times per week; i.p.) reduced the incidence and severity of abdominal aortic aneurysms induced by ANG II in mice, weakened the remodeling of the aortic wall, the inflammatory response and the formation of new blood vessels, and decreased the expression of MMP-2 and MMP-9, the level of MDA and the secretion of MCP-1 [7].
References:
[1] Ge J, Normant E, Porter JR, et al. Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of Hsp90. J Med Chem. 2006;49(15):4606-4615.
[2] Sun X, Bristol JA, Iwahori S, Hagemeier SR, Meng Q, Barlow EA, Fingeroth JD, Tarakanova VL, Kalejta RF, Kenney SC. Hsp90 inhibitor 17-DMAG decreases expression of conserved herpesvirus protein kinases and reduces virus production in Epstein-Barr virus-infected cells. J Virol. 2013 Sep;87(18):10126-38.
[3] Chang Y J, Huang C Y, Hung C S, et al. Glucose-regulated protein 78 mediates the therapeutic efficacy of 17-DMAG in colon cancer cells[J]. Tumor Biology, 2015, 36(6): 4367-4376.
[4] Mellatyar H, Talaei S, Pilehvar-Soltanahmadi Y, et al. Targeted cancer therapy through 17-DMAG as an Hsp90 inhibitor: Overview and current state of the art[J]. Biomedicine & Pharmacotherapy, 2018, 102: 608-617.
[5] Hertlein E, Wagner AJ, Jones J, et al. 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition. Blood. 2010;116(1):45-53.
[6] Kawano M, Tanaka K, Itonaga I, Iwasaki T, Kubota Y, Tsumura H. The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells. Oncol Res. 2023 Jul 21;31(5):631-643.
[7] Qi J, Yang P, Yi B, et al. Heat shock protein 90 inhibition by 17-DMAG attenuates abdominal aortic aneurysm formation in mice[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2015, 308(8): H841-H852.
17-DMAG (Alvespimycin) HCl是一种有效的Hsp90的抑制剂，其IC50值为62nM [1]。17-DMAG (Alvespimycin) HCl与Hsp90的ATP结合基序结合并抑制其蛋白质折叠保护活性，导致Hsp90的靶蛋白（如EGFR、AKT、突变p53和IKK）发生错误折叠和降解 [2]。17-DMAG (Alvespimycin) HCl具有抗肿瘤作用，可用于肺癌、肝癌和结肠癌等癌症研究 [3-4]。
在体外，17-DMAG (Alvespimycin) HCl（50-500nM; 24 or 48h）处理以剂量和时间依赖性方式显著导致慢性淋巴细胞白血病（CLL）细胞中Hsp90的靶蛋白IKK耗尽和半胱氨酸天冬氨酸依赖性凋亡，减少了NF-κB p50/p65 DNA的结合和NF-κB靶基因转录 [5]。17-DMAG (Alvespimycin) HCl（0-1000nM; 24h）处理以剂量依赖性方式抑制骨肉瘤细胞的增殖，并抑制MET蛋白的激活和细胞周期进程 [6]。
在体内，17-DMAG (Alvespimycin) HCl（10mg/kg/day; 5 times per week for 16 days; i.p.）治疗显著降低了TCL1-SCID移植小鼠模型血液中的白细胞数量，并延长了生存期 [5]。17-DMAG (Alvespimycin) HCl（5mg/kg/day; 3 times per week; i.p.）治疗降低了ANG II诱导的小鼠腹主动脉瘤的发生率和严重程度，减弱了主动脉壁的重塑、炎症反应和新生血管形成，并减少MMP-2和MMP-9的表达、MDA水平和MCP-1分泌 [7]。
| Kinase experiment [1]: | |
Preparation Method | Fluorescence polarization (FP)-based competition binding assay： |
Reaction Conditions | 0.1nM-10μM; 3h |
Applications | The IC50 value of 17-DMAG (Alvespimycin) HCl for human Hsp90 is 62nM. |
| Cell experiment [2]: | |
Cell lines | CD19-selected B cells from CLL patients |
Preparation Method | A total of 1 × 106 CD19-selected B cells from CLL patients were incubated for 24 or 48h in 17-DMAG (Alvespimycin) HCl, or vehicle. Apoptosis was determined by staining with annexin V-fluorescein isothiocyanate and propidium iodide (PI). After exposure to drugs, cells were washed with phosphate-buffered saline and stained in 1 time binding buffer. Cell death was assessed by flow cytometry using a Beckman-Coulter model EPICS XL cytometer. |
Reaction Conditions | 50nM-500nM; 24 or 48h |
Applications | 17-DMAG (Alvespimycin) HCl treatment significantly and dose- and time-dependently induces cysteine aspartate-dependent apoptosis in chronic lymphocytes. |
| Animal experiment [2]: | |
Animal models | SCID mice engrafted with TCL1 leukemia cells |
Preparation Method | SCID mice were housed in a clean environment and supplied with sterile food and water ad libitum. CD19-selected transformed B cells (1 × 106) from the spleen of a TCL1 transgenic mouse with active leukemia were engrafted by tail vein into an SCID mouse. Ten or 11 mice in each treatment group were treated with dimethyl sulfoxide (vehicle control) or 10mg/kg of 17-DMAG (Alvespimycin) HCl administered by intraperitoneal injection 5 times per week beginning 2 weeks after injection of leukemia cells. Blood was collected at various time points throughout treatment for RNA isolation and assessment of gene expression. |
Dosage form | 10mg/kg/day; 5 times per week for 16 days; i.p. |
Applications | 17-DMAG (Alvespimycin) HCl treatment significantly reduced the number of white blood cells in the blood of TCL1-SCID transplanted mouse models and prolonged their survival period. |
References: | |
| Cas No. | 467214-21-7 | SDF | |
| 别名 | 阿螺旋霉素盐酸盐; 17-DMAG hydrochloride; KOS-1022; BMS 826476 | ||
| 化学名 | [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-21-[2-(dimethylamino)ethylamino]-6-hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate;hydrochloride | ||
| Canonical SMILES | CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)C)OC)OC(=O)N)C)C)O)OC.Cl | ||
| 分子式 | C32H48N4O8.HCl | 分子量 | 653.21 |
| 溶解度 | ≥ 26.2mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5309 mL | 7.6545 mL | 15.309 mL |
| 5 mM | 306.2 μL | 1.5309 mL | 3.0618 mL |
| 10 mM | 153.1 μL | 765.5 μL | 1.5309 mL |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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Quality Control & SDS
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- Purity: >98.00%
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