| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
HSP90 (IC50 = 62 nM); GRP94 (IC50 = 65 nM)
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|---|---|
| ln Vitro |
Alvespimycin (17-DMAG) has an EC50 of 62 nM, making it a potent inhibitor of Hsp90. The human cancer cell lines SKBR3 and SKOV3, which overexpress the Hsp90 client protein Her2, are inhibited in their growth by alvespimycin (17-DMAG). This results in the down-regulation of Her2 and the induction of Hsp70, which is consistent with Hsp90 inhibition. In SKBR3 and SKOV3 cells, the EC50 values for Her2 degradation are 8 ± 4 nM and 46 ± 24 nM, respectively, while the EC50 values for Hsp70 induction are 4 ± 2 nM and 14 ± 7 nM, respectively[1]. Alvespimycin (17-DMAG) showed dose-dependent apoptosis (P<0.001 averaged over 24- and 48-hour time points) when compared to the vehicle control at concentrations ranging from 50 nM to 500 nM, which correspond to pharmacologically achievable doses. Alvespimycin (17-DMAG) exhibits time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells after an extended exposure period of 24 to 48 hours, which is comparable to that of many other agents. Alvespimycin (17-DMAG) also has significantly greater potency than 17-AAG after 24 and 48 hours of treatment[2].
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| ln Vivo |
Tumors are grown for two months prior to the initiation of intraperitoneal injections (i.p.) every four days for a month, using either 0, 5, 10, and 20 mg/kg Alvespimycin (17-DMAG) or 0, 50, 100, and 200 mg/kg Dipalmitoyl-radicicol. The animals receiving HSP90 inhibitor treatment had much smaller tumor volumes than the animals receiving vehicle control treatment, despite sample heterogeneity. In a gastrointestinal cancer animal model, HSP90 inhibitors have been demonstrated to cause liver toxicity. Yet, at 100 mg/kg, dipalmitoyl-radicicol reduces tumor size in a statistically significant way, whereas at 10 or 20 mg/kg, alvespimycin (17-DMAG) also significantly reduces tumor size[3].
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| Cell Assay |
The MTT assay is used to measure cytotoxicity. Alvespimycin, 17-AAG, or a vehicle are incubated for 24 or 48 hours with a total of 1×106 CD19-selected B cells from CLL patients. After adding MTT reagent, the plates are incubated for a further twenty-four hours, following which spectrophotometric measurement is performed. Using propidium iodide (PI) and annexin V-fluorescein isothiocyanate staining, apoptosis is identified. Cells are exposed to medications, and then they are cleaned in phosphate-buffered saline and stained once in binding buffer. Using flow cytometry, cell death is evaluated. The System II software package is used to analyze data. For every sample, ten thousand cells are counted. Changes in the potential of the mitochondrial membrane are evaluated by staining with the lipophilic cationic dye JC-1 and analyzing the results using flow cytometry[2].
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| Animal Protocol |
Mice: The mice used are CB-17/IcrHsd-Prkdc-SCID young male mice. A collagen solution is mixed with 1×105 BPH1 cells and 2.5×105 CAF per graft to create recombinant xenografts, which are then left to gel, covered with medium, and cultured for an entire night. The tumors are given eight weeks to form before being treated for four weeks with intraperitoneal injections of compounds in sesame oil every four days. The three different doses of dipalmitoyl-radicicol (50, 100, and 200 mg/kg) and Alvespimycin (5, 10 and 20 mg/kg) are administered. The mice are killed after a total of 12 weeks, their kidneys removed, the grafts cut in half, and their photos taken before the tissue is processed for histology. The measurements of the graft are taken, and the volume of the resulting tumor is computed using the formula volume=width × length × depth × π/6. This formula understates the volume of large, invasive tumors when compared to smaller, non-invasive tumors, suggesting a cautious approach to evaluating tumor volumes. Grafts that have been removed are embedded in paraffin, fixed in 10% formalin, and then subjected to immunohistochemistry.
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| References |
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| Molecular Formula |
C32H48N4O8
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|---|---|
| Molecular Weight |
616.756
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| Exact Mass |
616.3472
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| Elemental Analysis |
C, 62.32; H, 7.84; N, 9.08; O, 20.75
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| CAS # |
467214-20-6
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| Related CAS # |
Alvespimycin hydrochloride;467214-21-7
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| Appearance |
Solid powder
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| SMILES |
C[C@H]1C[C@@H]([C@@H]([C@H](/C=C(/[C@@H]([C@H](/C=C\C=C(\C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)/C)OC)OC(=O)N)\C)C)O)OC
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| InChi Key |
KUFRQPKVAWMTJO-LMZWQJSESA-N
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| InChi Code |
InChI=1S/C32H48N4O8/c1-18-14-22-27(34-12-13-36(5)6)24(37)17-23(29(22)39)35-31(40)19(2)10-9-11-25(42-7)30(44-32(33)41)21(4)16-20(3)28(38)26(15-18)43-8/h9-11,16-18,20,25-26,28,30,34,38H,12-15H2,1-8H3,(H2,33,41)(H,35,40)/b11-9-,19-10+,21-16+/t18-,20+,25+,26+,28-,30+/m1/s1
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| Chemical Name |
[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-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
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| Synonyms |
17-DMAG; KOS 1022; KOS-1022; KOS1022; Alvespimycin
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| HS Tariff Code |
2934.99.03.00
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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) |
DMSO: ~100 mg/mL (~162.1 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6214 mL | 8.1069 mL | 16.2138 mL | |
| 5 mM | 0.3243 mL | 1.6214 mL | 3.2428 mL | |
| 10 mM | 0.1621 mL | 0.8107 mL | 1.6214 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 |
| NCT00089362 | Completed | Other: pharmacological study Other: laboratory biomarker analysis |
Male Breast Cancer Recurrent Melanoma |
National Cancer Institute (NCI) |
July 2004 | Phase 1 |
| NCT00089271 | Completed | Other: laboratory biomarker analysis Drug: alvespimycin hydrochloride |
Intraocular Lymphoma Anaplastic Large Cell Lymphoma |
National Cancer Institute (NCI) |
July 2004 | Phase 1 |
| NCT00803556 | Completed | Drug: Alvespimycin Drug: Trastuzumab |
Solid Tumor Breast Cancer |
Bristol-Myers Squibb | January 2006 | Phase 1 |
| NCT00088868 | Completed | Drug: alvespimycin hydrochloride | Lymphoma Small Intestine Cancer |
National Institutes of Health Clinical Center (CC) |
June 2004 | Phase 1 |
| NCT00780000 | Terminated | Drug: Alvespimycin | Breast Cancer | Bristol-Myers Squibb | April 2008 | Phase 2 |
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