.cp_wz tabla {borde superior: 1px sólido #ccc; borde izquierdo: 1px sólido #ccc; } .cp_wz table td {borde derecho: 1px sólido #ccc; borde inferior: 1px sólido #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; relleno: 5px 0px 0px 5px;} \ n Peso molecular: 422,46 HS-173 es un potente inhibidor de PI3Kα con IC50 de 0,8 nM. \ n HS-173 muestra potentes efectos antiproliferativos en células T47D, SK-BR3 y MCF7 con IC50 de 0,6, 1,5 y 7,8 μM, respectivamente. HS-173 causa la supresión completa de la vía PI3K en líneas celulares cancerosas (Hep3B y SkBr3). Además, HS-173 induce la apoptosis celular al afectar la distribución del ciclo celular y activar las caspasas, y bloquea la angiogénesis inducida por VEGF in vitro. El tratamiento combinado con Sorafenib y HS-173 tiene un efecto anticancerígeno sinérgico sobre las células cancerosas de páncreas. HS-173 disminuye la formación de vasos sanguíneos en ratones. HS-173 atenúa notablemente el desarrollo de fibrosis hepática al bloquear la señalización de PI3K / Akt in vivo.
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PI3-Kinase assay
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The PI3K assay is performed using the Kinase-Glo Max luminescent kinase assay kit which quantifies the amount of ADP produced by the PI3K reaction. In brief, an active PI3K (100 ng) is preincubated with compound for 5 min in kinase reaction buffer (25 mM MOPS [pH 7.0], 5 mM MgCl2, and 1 mM EGTA) and 10 μg l-α-phosphatidylinositol (PI). Before addition of PI, it is sonicated with sonication buffer (25 mM MOPS [pH 7.0], 1 mM EGTA) in water for 20 min for allowing miscelle formation. Then reaction is started by the addition of 10 μM ATP and ran for 180 min. To terminate kinase reaction, same volume of Kinase-Glo Max buffer is added. After 10 min, the plates are then read on a GloMax plate reader for luminescence detection.
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Ensayo celular: [1]
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Cell lines
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T47D, SK-BR3, MCF7 cells
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Concentrations
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~50 μM
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Incubation Time
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48 hours
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Method
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Cell viability is performed by a MTT assay. Briefly, T47D cells are plated in 96-well plates for 24 h. Then, the medium is removed and cells were treated with either DMSO as a control or various concentrations of inhibitors. The final concentration of DMSO in the medium was ≤0.1% (v/v). After the cells are incubated for 48 h, 20 μL MTT solution (5 mg/mL) is added to each well for another 4 h at 37 °C. The formazan crystals that formed are dissolved in DMSO (100 μL/well) by constant shaking for 5 min. The plate is then read on a microplate reader at 540 nm. Three replicate wells are used for each analysis. The median inhibitory concentration (IC50, defined as the drug concentration at which cell growth is inhibited by 50%) is assessed from the dose−response curves. To assess the effect of compounds on cell proliferation, T47D cells are cultured with compound (0.1−100 μM) for 48 h before MTT analysis.
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Estudio con animales: [4]
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Animal Models
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Male BALB/c mice with CCl4-induced liver fibrosis
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Formulation
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Dissolved in DMSO, and then mixture (DMSO:PEG400:D.W. = 1:5:4).
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Dosages
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~20 mg/kg
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Administration
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p.o.
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Conversión de diferentes modelos de animales basados en BSA (valor basado en datos del Borrador de Directrices de la FDA)
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Species
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Baboon
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Dog
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Monkey
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Rabbit
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Guinea pig
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Rat
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Hamster
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Mouse
|
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Weight (kg)
|
12
|
10
|
3
|
1.8
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0.4
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0.15
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0.08
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0.02
|
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Body Surface Area (m2)
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0.6
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0.5
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0.24
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0.15
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0.05
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0.025
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0.02
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0.007
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Km factor
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20
|
20
|
12
|
12
|
8
|
6
|
5
|
3
|
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Animal A (mg/kg) = Animal B (mg/kg) multiplied by
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Animal B Km
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Animal A Km
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Por ejemplo, para modificar la dosis de resveratrol utilizada para un ratón (22,4 mg / kg) a una dosis basada en el BSA para una rata, multiplique 22,4 mg / kg por el factor Km para un ratón y luego divida por el factor Km para una rata. Este cálculo da como resultado una dosis equivalente para ratas de resveratrol de 11,2 mg / kg.
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Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×
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mouse Km(3)
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= 11.2 mg/kg
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|
rat Km(6)
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Información química
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Molecular Weight (MW)
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422.46
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Formula
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C21H18N4O4S
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CAS No.
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1276110-06-5
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Storage
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3 years -20℃Powder
|
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6 months-80℃in solvent (DMSO, water, etc.)
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Synonyms
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N/A
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Solubility (25°C) *
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In vitro
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DMSO
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84 mg/mL
heating
(198.83 mM)
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Water
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<1 mg/mL
(
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Ethanol
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<1 mg/mL
(
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* <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.
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Chemical Name
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ethyl 6-(5-(phenylsulfonamido)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxylate
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : PI3K / Akt / mTOR > Inhibidor de PI3K
