Geldanamycin

ArtNr	S2713-1000
Hersteller	Selleckchem
CAS-Nr.	30562-34-6
Menge	1 g
Quantity options	10 mg 1 g 10 mM/1 mL 5 mg 50 mg
Kategorie	Oncology Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Bladder Cancer Colorectal Cancer Breast Cancer Testicular & Prostate Cancer Uterine, Ovarian & Cervical Cancer
Typ	Inhibitors
Specific against	other
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
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	NSC 122750
Similar products	Geldanamycin
Lieferbar
Storage Conditions	2 years -80 in solvent
Molecular Weight	560, 64
Administration	Administered via i.p.
Animal Models	FRE/erbB-2 tumors in nu/nu mice
Cell lines	A2780 human ovarian cell line
Concentrations	0.001-10 uM
Dosages	50 mg/kg
Formulation	Geldanamycin is dissolved in DMSO.
IC50	1.2 M (Kd), 1.2 M (Kd), 1.2 M (Kd), 1.2 M (Kd), 1.2 M (Kd), 1.2 M (Kd)
In vitro	Geldanamycin binds in the ATP-binding site in the N-terminus domain of Hsp90s (residues 1-220). Geldanamycin inhibits the ATPase activity of Hsp90 in a dose-dependent manner. [1] Geldanamycin causes a dose-dependent G2 arrest and reversible inhibiton o f entry into the S phase in A2780 human ovarian cell line. This inhibition is accompanied by p53 increase and finally demonstrated to be p53 dependent. [2], Geldanamycin causes polyubiquitination and proteasomal degradation of the p185 receptor protein-tyrosin kinase and shows a IC50 with 70 nM. [3, 4] Geldanamycin is a typical anti-tumor reagent, shows a mean GI50 with 0.18 uM against the panel of 60 human tumor cell lines. [5]
In vivo	Geldanamycin (50 mg//kg) shows 30% inhibition on pl85-associated phosphotyrosine levels in FRE/erbB-2 mice. [6]
Incubation Time	3 hours
Kinase Assay	Isothermal Titration Calorimetry (ITC) of Nucelotide Binding, The titration experiments are performed using the MSC system. In each experiment, 16 aliquots of 15 uL of geldanamycin (300 uM in 1% DMSO) are injected into 1.3 mL of protein (31 uM in 20 mMTris-HCl, pH 7.5, 1 mMEDTA) at 25 C, and the resulting data are fit after subtracting the heats of dilution. Heats of dilution are 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 is observed. Titration data are 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 (deltaHC). Dissociation constants estimated for geldanamycin binding to intact yeast Hsp90 is 1.22 uM, and for binding to Hsp90 N-terminal domain is 0.78 uM. No meaningful heat is observed with binding to the C-terminal fragment.
Method	Exponentially growing cells are treated with Geldanamycin and at various times DNA synthesis is assessed 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 M) 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, cells are incubated with an anti-BrdUrd mouse monoclonal antibody followed by a fluorescein isothiocyanate (FITC)-linked goat anti-mouse IgG. Cells are stained for 30 minutes at room temperature with propidium iodide and analysed by flow cytometry using a Coulter EPICS Profile Analyzer.
Solubility (25C)	DMSO 112 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	Geldanamycin is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses.
Chemical Name	2-Azabicyclo[16.3.1]docosa-4, 6, 10, 18, 21-pentaene-3, 20, 22-trione, 9, 13-dihydroxy-8, 14, 19-trimethoxy-4, 10, 12, 16-tetramethyl-, 9-carbamate

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