1. Cell Cycle/DNA Damage
    Metabolic Enzyme/Protease
  2. HSP

Alvespimycin (Synonyms: 17-DMAG; NSC 707545)

Cat. No.: HY-10389
Handling Instructions

Alvespimycin is a potent inhibitor of Hsp90, binding to Hsp90 with an EC50 of 62 ± 29 nM.

For research use only. We do not sell to patients.

Alvespimycin Chemical Structure

Alvespimycin Chemical Structure

CAS No. : 467214-20-6

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Customer Review

Other Forms of Alvespimycin:

    Alvespimycin purchased from MCE. Usage Cited in: Friedrich-Alexander University Erlangen-Nuremberg. 2016.

    pJAK2 and JAK2 expression upon TGFβ stimulation and JAK inhibitors incubation. pJAK2 and JAK2 expression in healthy human fibroblasts after stimulation with TGFβ for 3 days and incubation with TG101209, 17-DMAG or Ruxolitinib.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Alvespimycin is a potent inhibitor of Hsp90, binding to Hsp90 with an EC50 of 62 ± 29 nM.

    IC50 & Target[1]

    HSP90

    62 nM (EC50)

    GRP94

    65 nM (EC50)

    In Vitro

    Alvespimycin is a potent inhibitor of Hsp90, binding to Hsp90 with an EC50 of 62 nM. Alvespimycin (17-DMAG) inhibits the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and causes down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition, for Her2 degradation with EC50 of 8 ± 4 nM and 46 ± 24 nM in SKBR3 and SKOV3 cells, respectively; for Hsp70 induction with EC50 of 4 ± 2 nM and 14 ± 7 nM in SKBR3 and SKOV3 cells, respectively[1]. Compared with the vehicle control, Alvespimycin dose-dependent apoptosis (P<0.001 averaged across 24- and 48-hour time points) at concentrations of 50 nM to 500 nM, which represent pharmacologically attainable doses. Similar to many other agents, Alvespimycin also demonstrates time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells with extended exposure from 24 to 48 hours. In addition, Alvespimycin is much more potent after 24 and 48 hours of treatment than 17-AAG[2].

    In Vivo

    The tumors are grown for two months before the start of i.p. injections every four days over one month with 0, 50, 100 and 200 mg/kg dipalmitoyl-radicicol or 0, 5, 10 and 20 mg/kg Alvespimycin. Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals. HSP90 inhibitors have been shown to cause liver toxicity in an animal model of gastrointestinal cancer. Nevertheless, the reduction in tumor size using dipalmitoyl-radicicol is statistically significant at 100 mg/kg, while Alvespimycin at either 10 or 20 mg/kg elicits a significant reduction in tumor size[3].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.6214 mL 8.1070 mL 16.2140 mL
    5 mM 0.3243 mL 1.6214 mL 3.2428 mL
    10 mM 0.1621 mL 0.8107 mL 1.6214 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [2]

    Alvespimycin (17-DMAG) is dissolved in DMSO and stored, and then diluted with appropriate media before use[2].

    MTT assays are performed to determine cytotoxicity. A total of 1×106 CD19-selected B cells from CLL patients are incubated for 24 or 48 hours in Alvespimycin, 17-AAG, or vehicle. 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). After exposure to drugs, cells are washed with phosphate-buffered saline and stained in 1 time binding buffer. Cell death is assessed by flow cytometry. Data are analyzed with the System II software package. A total of 10000 cells are counted for each sample. Mitochondrial membrane potential changes are assessed by staining with the lipophilic cationic dye JC-1 and analysis by flow cytometry[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3]

    Alvespimycin is prepared in sesame oil (Mice)[3].

    Mice[3]
    Young male CB-17/IcrHsd-Prkdc-SCID mice are used. Recombinant xenografts are made by mixing 1×105 BPH1 cells and 2.5×105 CAF per graft in collagen solution, allowed to gel, covered with medium and cultured overnight. Tumors are allowed to form over eight weeks, and then treated for four weeks with three different doses of dipalmitoyl-radicicol (50, 100 and 200 mg/kg) and Alvespimycin (5, 10 and 20 mg/kg) via intraperitoneal injections of compounds in sesame oil every four days. After 12 weeks in total, the mice are sacrificed, their kidneys resected, grafts cut in half and photographed before processing for histology. Graft dimensions are measured and the resultant tumour volume is calculated using the formula; volume=width × length × depth × π/6. This formula represents a conservative approach to evaluate tumour volumes, as it understates the volume of large, invasive tumours compared with smaller, non-invasive tumours. Resected grafts are fixed in 10% formalin, embedded in paraffin and processed for immunohistochemistry. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    616.75

    Formula

    C₃₂H₄₈N₄O₈

    CAS No.

    467214-20-6

    SMILES

    C/C1=C\C=C/[[email protected]@H]([[email protected]](/C(C)=C/[[email protected]@H]([[email protected]]([[email protected]](C[[email protected]@H](CC(C(C(NC1=O)=CC2=O)=O)=C2NCCN(C)C)C)OC)O[H])C)OC(N)=O)OC

    Storage

    Please store the product under the recommended conditions in the Certificate of Analysis.

    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Product Name:
    Alvespimycin
    Cat. No.:
    HY-10389
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