Chine Geldanamycine 30562-34-6 Fabricants

Les dernières alertes produit

Geldanamycine 30562-34-6

Informations de base

Description du produit .cp_wz table {border-top : 1px solide #ccc;border-left:1px solide #ccc ; } .cp_wz table td{border-right : 1px solide #ccc ; border-bottom : 1px solide #ccc ; remplissage : 5px 0px 0px 5px;} .cp_wz table th {border-right : 1px solid #ccc;border-bottom : 1px solid #ccc ; rembourrage : 5px 0px 0px 5px ;}
Poids moléculaire :
560,64 La geldanamycine est un inhibiteur HSP90 naturel existant avec un Kd de 1,2 M, qui perturbe spécifiquement l'association récepteur des glucocorticoïdes (GR)/HSP.
Activité biologique La geldanamycine se lie à l'ATP- site de liaison dans le domaine N-terminal des Hsp90 (résidus 1-220). La geldanamycine inhibe l'activité ATPase de Hsp90 de manière dose-dépendante. La geldanamycine provoque un arrêt G2 dose-dépendant et une inhibition réversible de l'entrée en phase S dans la lignée cellulaire ovarienne humaine A2780. Cette inhibition s'accompagne d'une augmentation de p53 et a finalement été démontrée comme dépendante de p53. La geldanamycine provoque une polyubiquitination et une dégradation protéasomale de la protéine-tyrosine kinase du récepteur pl85 et présente une CI50 de 70 nM. La geldanamycine est un réactif anti-tumoral typique, montre un GI50 moyen avec 0,18 M contre le panel de 60 lignées cellulaires tumorales humaines. La geldanamycine (50 mg//kg) présente une inhibition de 30 % sur les niveaux de phosphotyrosine associés à pl85 chez les souris FRE/erbB-2. Protocole (uniquement pour référence) Dosage de la kinase : [1]

Isothermal Titration Calorimetry (ITC) of Nucelotide Binding	The titration experiments are performed using the MSC system. In each experiment, 16 aliquots of 15 μL of geldanamycin (300 μM in 1% DMSO) are injected into 1.3 mL of protein (31 μM 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 (ΔH°). Dissociation constants estimated for geldanamycin binding to intact yeast Hsp90 is 1.22 μM, and for binding to Hsp90 N-terminal domain is 0.78 μM. No meaningful heat is observed with binding to the C-terminal fragment.
ATPase Assay	The ATPase assay is based on a regenerating coupled enzyme assay in which the phosphorylation of ADP by pyruvate kinase at the expense of phosphoenolpyruvate is coupled to the reduction of the resulting pyruvate by lactate dehydrogenase at the expense of

Isothermal Titration Calorimetry (ITC) of Nucelotide Binding

The titration experiments are performed using the MSC system. In each experiment, 16 aliquots of 15 μL of geldanamycin (300 μM in 1% DMSO) are injected into 1.3 mL of protein (31 μM 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 (ΔH°). Dissociation constants estimated for geldanamycin binding to intact yeast Hsp90 is 1.22 μM, and for binding to Hsp90 N-terminal domain is 0.78 μM. No meaningful heat is observed with binding to the C-terminal fragment.

ATPase Assay

The ATPase assay is based on a regenerating coupled enzyme assay in which the phosphorylation of ADP by pyruvate kinase at the expense of phosphoenolpyruvate is coupled to the reduction of the resulting pyruvate by lactate dehydrogenase at the expense of

Dosage cellulaire : [2]

Cell lines	A2780 human ovarian cell line
Concentrations	0.001-10 μM
Incubation Time	3 hours
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 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, 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.

Étude animale : [6]

Animal Models	FRE/erbB-2 tumors in nu/nu mice
Formulation	Geldanamycin is dissolved in DMSO.
Dosages	50 mg/kg
Administration	Administered via i.p.

Conversion de différents animaux modèles sur la base de la BSA (valeur basée sur les données des lignes directrices provisoires de la FDA)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

Par exemple, pour modifier la dose de resvératrol utilisée pour une souris (22,4 mg/kg) à une dose basée sur la BSA pour un rat, multiplier 22,4 mg/kg par le facteur Km pour une souris puis diviser par le facteur Km pour un rat. Ce calcul donne une dose équivalente chez le rat pour le resvératrol de 11,2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Informations chimiques

Molecular Weight (MW)	560.64
Formula	C29H40N2O9
CAS No.	30562-34-6

Storage	3 years -20℃Powder
Storage	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms	NSC 122750

Solubility (25°C) *	In vitro	DMSO	100 mg/mL heating (178.36 mM)
		Water	<1 mg/mL (
		Ethanol	<1 mg/mL (
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.