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Geldanamycin is a benzoquinone ansamycin antibiotic that binds to Hsp90 (Heat Shock Protein 90) and alters its function. Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a compound candidate (namely, hepatotoxicity) that have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position:17-AAG,17-DMAG.
| Cell Experiment | |
|---|---|
| Cell lines | A2780 human ovarian cell line |
| Preparation method | Treating exponentially growing cells with Geldanamycin and assessing at various times DNA synthesis by incorporation of bromodeoxyuridine (BrdUrd) and flow cytometric analysis. No marked difference in total cell number is noted during this time course for treated and untreated cultures. BrdUrd (10 μM) is incorporated over a 4-h incubation period at 37 °C and cells are harvested and fixed in 70% ethanol. After denaturation of the DNA with 2 N HC1, incubating cells with an anti-BrdUrd mouse monoclonal antibody followed by a fluorescein isothiocyanate (FITC)-linked goat anti-mouse IgG. Staining cells for 30 minutes at room temperature with propidium iodide and analysing by flow cytometry using a Coulter EPICS Profile Analyzer. |
| Concentrations | 0.001-10 μM |
| Incubation time | 3 hours |
| Animal Experiment | |
|---|---|
| Animal models | FRE/erbB-2 tumors in nu/nu mice |
| Formulation | Geldana50 mg/kgmycin is dissolved in DMSO. |
| Dosages | 50 mg/kg |
| Administration | Administered via i.p. |
| Molecular Weight | 560.64 |
| Formula | C29H40N2O9 |
| CAS Number | 30562-34-6 |
| Solubility (25°C) | DMSO 39 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related HSP Products |
|---|
| NCT-58
NCT-58 is a potent inhibitor of C-terminal HSP90. |
| Gedunin
Gedunin is a limonoid with anti-cancer, anti-viral, anti-inflammatory and insecticidal activities. |
| VER-49009
VER-49009 is a Hsp90 inhibitor, with an IC50 of 25 nM and a Kd of 78 nM. |
| YUM70
YUM70 is a potent and selective inhibitor of glucose-regulated protein 78 (GRP78), with an IC50 of 1.5 μM for inhibiting GRP78 ATPase activity. YUM70 induces endoplasmic reticulum stress-mediated apoptosis in pancreatic cancer. |
| Hsp70-derived octapeptide
Hsp70-derived octapeptide is a conserved octapeptide of the C-terminal end of Hsp70, which physically interacts with tetratricopeptide repeat (TPR) motifs. |
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