CP-91149 licenciado pela Pfizer

.cp_wz table {border-top: 1px solid #ccc; border-left: 1px solid #ccc; } .cp_wz table td {border-right: 1px solid #ccc; borda inferior: 1px sólido #ccc; preenchimento: 5px 0px 0px 5px;} .cp_wz tabela th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; preenchimento: 5px 0px 0px 5px;} \ n Peso molecular: \ n 399,87 CP-91149 é um inibidor seletivo de glicogênio fosforilase (GP) com IC50 de 0,13 μM na presença de glicose, 5 a 10 vezes menos potente na ausência de glicose. \ n Atividade biológica

Description	CP-91149 is a selective glycogen phosphorylase (GP) inhibitor with IC50 of 0.13 μM in the presence of glucose, 5- to 10-fold less potent in the absence of glucose.
Targets	Glycogen phosphorylase (GP) [1]
IC50	0.13 μM
In vitro	CP-91149 displays 200-fold higher inhibitory activity against human liver glycogen phosphorylase a (HLGPa) than caffeine (IC50 = 26 μM). CP-91149 (10-100 μM) inhibits glucagon-stimulated glycogenolysis in isolated rat hepatocytes in a dose-dependent manner, and in primary human hepatocytes with IC50 of ~2.1 μM. [1] CP-91149 also potently inhibits the activities of human muscle phosphorylase a and b with IC50 of 0.2 μM and ~0.3 μM, respectively. CP-91149 treatment at 2.5 μM induces inactivation of phosphorylase and sequential activation of glycogen synthase in hepatocytes, and increases glycogen synthesis by 7-fold at 5 mM glucose and by 2-fold at 20 mM glucose. CP-91149 can partially counteract the effects of phosphorylase overexpression. [2] CP-91149 also potently inhibits brain GP with IC50 of 0.5 μM in A549 cells. CP-91149 treatment at 10-30 μM causes significant glycogen accumulation in A549 and HSF55 cells. CP-91149 treatment increases G1-phase cells with a significant reduction of the S-phase population in HSF55 cells, correlated with increased expression of p21 and p27. [3] CP-91149 also promotes the dephosphorylation and activation of GS (glycogen synthase) in non-engineered or GP-overexpressing cultured human muscle cells, but exclusively in glucose-deprived cells. [4]
In vivo	Oral administration of CP-91149 to diabetic ob/ob mice at 25-50 mg/kg causes rapid (3 hours) glucose lowering by 100-120 mg/dl without producing hypoglycemia, resulting from inhibition of glycogenolysis in vivo. CP-91149 treatment does not lower glucose levels in normoglycemic, nondiabetic mice. [1] In the non-fasted Goto-Kakizaki (GK) rats, administration of CP-91149 in combination with CS-917 suppresses hepatic glycogen reduction by CS-917 and decreases plasma glucose more than single administration of CS-917. [5]
Features

Ensaio de cinase de protocolo (apenas para referência): [1]

Phosphorylase enzyme assay

Human liver glycogen phosphorylase a (HLGPa, 85 ng) activity is measured in the direction of glycogen synthesis by the release of phosphate from glucose-1-phosphate at 22°C in 100 μL of buffer containing 50 mM Hepes (pH 7.2), 100 mM KCl, 2.5 mM EGTA, 2.5 mM MgCl2, 0.5 mM glucose-1-phosphate, and 1 mg/mL glycogen. Phosphate is measured at 620 nm, 20 minutes after the addition of 150 μL of 1 M HCl containing 10 mg/mL ammonium molybdate and 0.38 mg/mL malachite green. Increasing concentrations of CP-91149 are added to the assay in 5 μL of 14% DMSO.

Ensaio de células: [3]

Cell lines	HSF55 and T98G
Concentrations	Dissolved in DMSO, final concentrations ~50 μM
Incubation Time	72 hours
Method	Cells are exposed to various concentrations of CP-91149 for 72hours. Viability is determined with manual cell counts following staining with trypan blue exclusion assay. Cells are fixed with 70% ethanol. DNA is stained with propidium iodide and the intensity of fluorescence is measured using a Becton-Dickinson flow cytometer at 488nm for excitation and at 650nm for emission. The cell cycle profile is analyzed using Modifit's Sync Wizard.

Estudo Animal: [1]

Animal Models	Obese, diabetic male C57BL/6J-Lep(ob/ob) mice and their lean, nondiabetic C57BL/6J-/+ littermates
Formulation	Formulated in vehicle consisting of either 0.25% (wt/vol) methyl cellulose in water or 0.1% Pluronic P105 Block Copolymer Surfactant in 0.1% saline
Dosages	~50 mg/kg
Administration	Orally
Solubility	0.5% methylcellulose/0.2% Tween 80, 5 mg/mL
* 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.

Conversão de diferentes modelos de animais com base em BSA (valor com base em dados das diretrizes preliminares da 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

Por exemplo, para modificar a dose de resveratrol usada para um camundongo (22,4 mg / kg) para uma dose baseada na BSA para um rato, multiplique 22,4 mg / kg pelo fator Km para um camundongo e, em seguida, divida pelo fator Km para um rato. Este cálculo resulta em uma dose equivalente de rato para o resveratrol 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)

1 Referências [1] Martin WH, et al. Proc Natl Acad Sci USA, 1998, 95 (4), 1776-1781. [2] Aiston S, et al. J Biol Chem, 2001, 276 (26), 23858-23866. [3] Schnier JB, et al. Biochem Biophys Res Commun, 2003, 309 (1), 126-134. [4] Lerín C, et al. Biochem J, 2004, 378 (Pt 3), 1073-107 [5] Yoshida T, et al. J Pharmacol Sei, 2011, 115 (3), 329-335. Download de informações químicas CP-91149 SDF

Molecular Weight (MW)	399.87
Formula	C21H22ClN3O3
CAS No.	186392-40-5

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

Solubility (25°C) *	In vitro	DMSO	80 mg/mL (200.06 mM)
		Water	<1 mg/mL (
		Ethanol	<1 mg/mL (
	In vivo	0.5% methylcellulose/0.2% Tween 80	5 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.

Chemical Name	5-chloro-N-((2S,3R)-4-(dimethylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-1H-indole-2-carboxamide

Calculadora de molaridade Calculadora de diluição Calculadora de peso molecular Área de pesquisa

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.39987	3.9987	7.9974	11.9961

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Grupo de Produto : Outros > Inibidor de Fosforilase