Chine Statistique 19983-44-9 Fabricants

Statistique 19983-44-9

Informations de base

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Poids moléculaire :
211.19 Stattic, la première petite molécule non peptidique, inhibe puissamment l'activation de STAT3 et la translocation nucléaire avec une IC50 de 5,1 M, hautement sélective par rapport à STAT1.
Activité biologique Stattic inhibe la liaison de un peptide contenant de la phosphotyrosine dérivé du récepteur gp130 au domaine STAT3 SH2 d'une manière fortement dépendante de la température. La statistique n'a qu'un effet très faible sur la liaison d'un peptide tyrosine phosphorylé au domaine SH2 de la tyrosine kinase Lck. Et il n'inhibe pas la dimérisation de deux autres facteurs de transcription dimères (c-Myc/Max et Jun/Jun). Il inhibe également les phosphopeptides marqués à la fluorescéine dans les domaines SH2 de STAT1 et STAT5b. Stattic inhibe sélectivement la liaison à l'ADN des homodimères STAT3 à une concentration de 10 M. Inhibe la phosphorylation cellulaire de STAT3 à Tyr705 avec peu d'effet sur la phosphorylation de STAT1 à Tyr701 (dans les cellules HepG2) ou la phosphorylation de JAK1, JAK2 et c-Src (dans les cellules MDA-MB-231 et MDA-MB-235S). Stattic augmente le taux d'apoptose des lignées cellulaires de cancer du sein dépendantes de STAT3. Protocole (uniquement pour référence) Dosage de la kinase : [1]

High-Throughput Screening and Fluorescence Polarization Assays	Screening is performed at approximately 30 °C. The specificity of screening hits is validated in analogous assays for binding of the test compounds to the SH2 domains of STAT1, STAT5, and Lck. The final concentration of buffer components used for all FP assays is 10 mM HEPES (pH 7.5), 1 mM EDTA, 0.1% Nonidet P-40, 50 mM NaCl, and 10% DMSO. The absence of dithiothreitol is essential for inhibitory activity. The sequences of the peptides are: STAT3, 5-carboxyfluorescein-GY(PO3H2)LPQTV-NH2; STAT1, 5-carboxyfluorescein-GY(PO3H2)DKPHVL; STAT5, 5-carboxyfluorescein-GY(PO3H2)LVLDKW; and Lck, 5-carboxyfluorescein-GY(PO3H2)EEIP. For specificity analysis at 30 °C, proteins are used at 150 nM (STAT1, STAT3, and STAT5). For specificity analysis at 37 °C, proteins are used at 370 nM (STAT3) or 100 nM (Lck). Proteins are incubated with test compounds in Eppendorf tubes at the indicated temperatures for 60 min prior addition of the respective 5-carboxyfluorescein labeled peptides (final concentration: 10 nM). Before measurement at room temperature, the mixtures are allowed to equilibrate for at least 30 min. Test compounds are used at the indicated concentrations diluted from a 20× stock in DMSO. Binding curves and inhibition curves are fitted with SigmaPlot. All competition curves are repeated three times in independent experiment

High-Throughput Screening and Fluorescence Polarization Assays

Screening is performed at approximately 30 °C. The specificity of screening hits is validated in analogous assays for binding of the test compounds to the SH2 domains of STAT1, STAT5, and Lck. The final concentration of buffer components used for all FP assays is 10 mM HEPES (pH 7.5), 1 mM EDTA, 0.1% Nonidet P-40, 50 mM NaCl, and 10% DMSO. The absence of dithiothreitol is essential for inhibitory activity. The sequences of the peptides are: STAT3, 5-carboxyfluorescein-GY(PO3H2)LPQTV-NH2; STAT1, 5-carboxyfluorescein-GY(PO3H2)DKPHVL; STAT5, 5-carboxyfluorescein-GY(PO3H2)LVLDKW; and Lck, 5-carboxyfluorescein-GY(PO3H2)EEIP. For specificity analysis at 30 °C, proteins are used at 150 nM (STAT1, STAT3, and STAT5). For specificity analysis at 37 °C, proteins are used at 370 nM (STAT3) or 100 nM (Lck). Proteins are incubated with test compounds in Eppendorf tubes at the indicated temperatures for 60 min prior addition of the respective 5-carboxyfluorescein labeled peptides (final concentration: 10 nM). Before measurement at room temperature, the mixtures are allowed to equilibrate for at least 30 min. Test compounds are used at the indicated concentrations diluted from a 20× stock in DMSO. Binding curves and inhibition curves are fitted with SigmaPlot. All competition curves are repeated three times in independent experiment

Dosage cellulaire : [2]

Cell lines	Ly3 cells
Concentrations	~2.5 μM
Incubation Time	48 h
Method	MTS

Étude animale : [2]

Animal Models	Ly3 parental NOD/SCID IL2R null xenograft
Formulation
Dosages	3.75 mg/kg every day
Administration	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)	211.19
Formula	C8H5NO4S
CAS No.	19983-44-9

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

Solubility (25°C) *	In vitro	DMSO	42 mg/mL (198.87 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.