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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
17-DMAG (Alvespimycin, NSC-707545, BMS-826476 HCl, KOS-1022) HCl, the hydrochloride salt of 17-DMAG, is a novel and potent HSP90 (heat shock protein 90) inhibitor with potential antineoplastic activity. It inhibits HSP90 with an IC50 of 62 nM in a cell-free assay. 17-DMAG is an analogue of the anticancer benzoquinone antibiotic geldanamycin. 17-DMAG binds to HSP90, subsequently, the function of Hsp90 is inhibited, leading to the degradation and depletion of its client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction.
| ln Vitro |
Human cancer cell lines SKBR3 and SKOV3, which overexpress the Hsp90 protein Her2, are inhibited in their proliferation by alvespimycin hydrochloride (17-DMAG hydrochloride; KOS-1022; BMS 826476). This results in the downregulation of Her2 and the upregulation of Hsp70. The EC50 values for Hsp90 inhibition on Her2 degradation were 8±4 nM and 46±24 nM in SKBR3 and SKOV3 cells, respectively. Similarly, the EC50 values for Hsp70 induction were 4±2 nM and 14±7 nM in SKBR3 and SKOV3 cells, respectively [1]. At concentrations of 50 nM to 500 nM, which correspond to pharmacologically attainable levels, 17-DMAG exhibited dose-dependent apoptosis (mean P<0.001 for the 24- and 48-hour time periods) in comparison to the vehicle control. In chronic lymphocytic leukemia (CLL) cells treated for 24 to 48 hours, alvespimycin hydrochloride also showed time-dependent apoptosis (P < 0.001, mean of all doses), just like many other medications. Additionally, after 24 and 48 hours of treatment, Alvespimycin hydrochloride was more effective than 17-AAG[2].
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| ln Vivo |
Intraperitoneal injections of 0, 5, 10, and 20 mg/kg 17-DMAG or 0, 50, 100, and 200 mg/kg dipalmitoylradiol were given every four days for a month prior to the formation of the tumor. mice treated with HSP90 inhibitors had far smaller tumor sizes than mice treated with vehicle control, notwithstanding sample heterogeneity. It has been demonstrated that HSP90 inhibitors produce hepatotoxicity in gastrointestinal cancer animal models. However, 100 mg/kg of dipalmitoylradiol greatly decreased tumor size, and 10 or 20 mg/kg of 17-DMAG did the same [3].
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| References |
[1]. Ge J, 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 Jul 27;49(15):4606-15.
[2]. Hertlein E, 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 Jul 8;116(1):45-53. [3]. Henke A, et al. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90. Cancers (Basel). 2016 Aug 24;8(9). pii: E77 |
| Molecular Formula |
C32H48N4O8.HCL
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|---|---|
| Molecular Weight |
653.21
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| CAS # |
467214-21-7
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| Related CAS # |
Alvespimycin;467214-20-6
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| SMILES |
NC(O[C@@H](/C(C)=C/[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC1=C2OCCN(C)C)[C@@H](OC)/C=C\C=C(C)\C(NC(C1=O)=CC2=O)=O)=O.[H]Cl
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| InChi Key |
BXRBNELYISPBKT-BJGZLATJSA-N
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| InChi Code |
InChI=1S/C32H47N3O9.ClH/c1-18-14-22-28(38)23(17-24(36)30(22)43-13-12-35(5)6)34-31(39)19(2)10-9-11-25(41-7)29(44-32(33)40)21(4)16-20(3)27(37)26(15-18)42-8;/h9-11,16-18,20,25-27,29,37H,12-15H2,1-8H3,(H2,33,40)(H,34,39);1H/b11-9-,19-10+,21-16+;/t18-,20+,25+,26+,27-,29+;/m1./s1
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| Chemical Name |
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2-(dimethylamino)ethoxy)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate hydrochloride
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| Synonyms |
Alvespimycin; Alvespimycin HCl; Alvespimycin Hydrochloride; NSC 707545; BMS 826476 HCl; KOS 1022; NSC-707545; BMS-826476 HCl; KOS-1022; NSC707545; BMS826476 HCl; KOS1022
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5309 mL | 7.6545 mL | 15.3090 mL | |
| 5 mM | 0.3062 mL | 1.5309 mL | 3.0618 mL | |
| 10 mM | 0.1531 mL | 0.7655 mL | 1.5309 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00089271 | Completed | Drug: alvespimycin hydrochloride | Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma |
National Cancer Institute (NCI) | July 2004 | Phase 1 |
| NCT01126502 | Terminated | Drug: alvespimycin hydrochloride | B-cell Chronic Lymphocytic Leukemia Prolymphocytic Leukemia |
National Cancer Institute (NCI) | May 2010 | Phase 2 |
| NCT00089362 | Completed | Drug: alvespimycin hydrochloride | Male Breast Cancer Recurrent Adenoid Cystic Carcinoma of the Oral Cavity |
National Cancer Institute (NCI) | July 2004 | Phase 1 |
| NCT00088868 | Completed | Drug: alvespimycin hydrochloride | Lymphoma Small Intestine Cancer |
National Institutes of Health Clinical Center (CC) |
June 2004 | Phase 1 |
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