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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 |
|---|
| BIIB021
BIIB021 (CNF2024) is an orally available synthetic non-ansamycin Hsp90 inhibitor with ki value of 1.7nM. |
| CUDC-305
CUDC-305 is a heat shock protein 90 (HSP90) inhibitor of the novel imidazopyridine class, with IC50 values of 100 and 103 nM for HSP90α and HSP90β, respectively. |
| Ganetespib
Ganetespib (STA-9090) is a potent synthetic small molecule inhibitor of Hsp90 with potential antineoplastic activity. |
| Luminespib (AUY922)
Luminespib (AUY922) is a small molecule Heat Shock Protein 90 (HSP90) inhibitor with IC50 values of 13 and 21 nM for HSP90α and HSP90β respectively. |
| NVP-HSP990
NVP-HSP990 is an orally bioavailable inhibitor of human heat-shock protein 90 (Hsp90) with IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, respectively. NVP-HSP990 has potential antineoplastic activity. |
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