17-DMAG (Alvespimycin) HCl |
| Catalog No.GC13044 |
17-DMAG(알베스피마이신) HCl(17-DMAG 염산염; KOS-1022; BMS 826476)은 62&7#177;29nM의 EC50으로 Hsp90에 결합하는 Hsp90의 강력한 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Chemical Name | [(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 | ||
| Formula | C32H48N4O8.HCl | M.Wt | 653.21 |
| Solubility | ≥ 26.2mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 7 reference(s) in Google Scholar.)
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