.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: 422,46 HS-173 é um potente inibidor de PI3Kα com IC50 de 0,8 nM. \ n HS-173 mostra efeitos antiproliferativos potentes em células T47D, SK-BR3 e MCF7 com IC50 de 0,6, 1,5 e 7,8 μM, respectivamente. HS-173 causa supressão completa da via PI3K em linhas de células cancerosas (Hep3B e SkBr3). Além disso, o HS-173 induz a apoptose celular, afetando a distribuição do ciclo celular e ativando caspases, e bloqueia a angiogênese induzida por VEGF in vitro. O tratamento combinado com Sorafenibe e HS-173 tem um efeito anticâncer sinérgico nas células do câncer pancreático. HS-173 diminui a formação de vasos sanguíneos em camundongos. HS-173 atenua marcadamente o desenvolvimento de fibrose hepática, bloqueando a sinalização 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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Ensaio de células: [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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Estudo Animal: [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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Conversão de diferentes modelos de animais com base em BSA (valor com base em dados das diretrizes preliminares da 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)
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12
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10
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3
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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
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20
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12
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12
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8
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6
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5
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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 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.
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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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Informação 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 molaridade Calculadora de diluição Calculadora de peso molecular
Grupo de Produto : PI3K / Akt / mTOR > Inibidor PI3K
