Geldanamycin (Synonyms: NSC 122750) |
Catalog No.GC16361 |
Binds Hsp90 and GRP94, inhibits growth of cancer cells
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 30562-34-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment [1]: | |
Isothermal titration calorimetry (ITC) of nucelotide binding |
The titration experiments were performed using the MSC system. In each experiment, 16 aliquots of 15 μL of Geldanamycin (300 μM in 1% DMSO) were injected into 1.3 mL of protein (31 μM in 20 mM Tris-HCl, pH 7.5, 1 mM EDTA) at 25°C, and the resulting data were fit after subtracting the heats of dilution. Heats of dilution were determined in separate experiments from addition of Geldanamycin into buffer and buffer into protein. No evidence for binding of DMSO in the nucleotide binding site was observed. Titration data were fit using a nonlinear least-squares curve-fitting algorithm with three floating variables: stoichiometry, binding constant (Kb = 1/Kd), and change of enthalpy of interaction (ΔH°). The dissociation constant estimated for Geldanamycin binding to intact yeast Hsp90 was 1.22 μM, and for binding to Hsp90 N-terminal domain was 0.78 μM. No meaningful heat was observed with binding to the C-terminal fragment. |
Cell experiment [2]: | |
Cell lines |
A2780 cells |
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions |
0.001 ~ 10 μM; 3 hrs |
Applications |
In human ovarian cell line A2780, Geldanamycin caused a dose-dependent G2 arrest and reversible inhibiton of entry into the S phase. |
Animal experiment [3]: | |
Animal models |
Mice bearing FRE/erbB-2 tumors |
Dosage form |
50, 100, 200 and 400 mg/kg; i.p.; b.i.d., for 5 days |
Applications |
In mice bearing FRE/erbB-2 tumors, Geldanamycin (50 mg/kg) shows 30% inhibition on p185-associated phosphotyrosine levels. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Roe SM, Prodromou C, O'Brien R, Ladbury JE, Piper PW, Pearl LH. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem. 1999 Jan 28;42(2):260-6. [2]. McIlwrath AJ, Brunton VG, Brown R. Cell-cycle arrest and p53 accumulation induced by geldanamycin in human ovarian tumour cells. Cancer Chemother Pharmacol. 1996;37(5):423-8. [3]. Schnur RC, Corman ML, Gallaschun RJ, Cooper BA, Dee MF, Doty JL, Muzzi ML, Moyer JD, DiOrio CI, Barbacci EG, et al. Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives. J Med Chem. 1995 Sep 15;38(19):3806-12. |
Geldanamycin, a crystalline antimicrobial compound derived from the culture filtrates of Streptomyces hygroscopicus var. geldanus var. nova., is a potent and specific inhibitor of heat shock protein 90 (Hsp90) that specifically binds to the unique ATP binding pocket of Hsp90 in a stable and pharmacologically specific manner. As an antimicrobial agent, geldanamycin exhibits moderate activity against protozoa, bacteria and fungi as well as parasite Syphacia oblevata and cell cultures of L-1210 and KB. Recent studies have shown that geldanamycin also inhibits the function of glucocorticoid receptor and endothelium-dependent relaxation of the rat aorta, mesentery and middle artery.
Reference
[1].Bucci M, Roviezzo F, Cicala C, Sessa WC, Cirino G. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucocorticoid receptor in vivo. Br J Pharmacol. 2000; 131(1): 13-16.
[2].DeBoer C, Meulman PA, Wnuk RJ, Peterson DH. Geldanamycin, a new antibiotic. J Antibiot (Tokyo). 1970; 23(9):442-447.
Cas No. | 30562-34-6 | SDF | |
Synonyms | NSC 122750 | ||
Chemical Name | [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate | ||
Canonical SMILES | CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)OC)C)OC)OC(=O)N)C)C)O)OC | ||
Formula | C29H40N2O9 | M.Wt | 560.6 |
Solubility | ≥ 16.9 mg/mL in DMSO | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.7838 mL | 8.919 mL | 17.838 mL |
5 mM | 0.3568 mL | 1.7838 mL | 3.5676 mL |
10 mM | 0.1784 mL | 0.8919 mL | 1.7838 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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