.cp_wz table {border-top: твердое тело 1px #ccc; border-left: твердое тело 1px #ccc; } .cp_wz таблица td {border-right: 1px solid #ccc; нижняя граница: сплошной 1px #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} \ n Молекулярный вес: 422,46 HS-173 - мощный ингибитор PI3Kα с IC50 0,8 нМ. \ n HS-173 проявляет сильные антипролиферативные эффекты в клетках T47D, SK-BR3 и MCF7 с IC50 0,6, 1,5 и 7,8 мкМ соответственно. HS-173 вызывает полное подавление пути PI3K в линиях раковых клеток (Hep3B и SkBr3). Более того, HS-173 индуцирует апоптоз клеток, влияя на распределение клеточного цикла и активируя каспазы, и блокирует VEGF-индуцированный ангиогенез in vitro. Комбинированное лечение сорафенибом и HS-173 оказывает синергетическое противораковое действие на раковые клетки поджелудочной железы. HS-173 уменьшает образование кровеносных сосудов у мышей. HS-173 заметно ослабляет развитие фиброза печени, блокируя передачу сигналов PI3K / Akt in vivo.
|
PI3-Kinase assay
|
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.
|
Клеточный анализ: [1]
|
Cell lines
|
T47D, SK-BR3, MCF7 cells
|
|
Concentrations
|
~50 μM
|
|
Incubation Time
|
48 hours
|
|
Method
|
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.
|
Исследование на животных: [4]
|
Animal Models
|
Male BALB/c mice with CCl4-induced liver fibrosis
|
|
Formulation
|
Dissolved in DMSO, and then mixture (DMSO:PEG400:D.W. = 1:5:4).
|
|
Dosages
|
~20 mg/kg
|
|
Administration
|
p.o.
|
Конверсия различных модельных животных на основе BSA (значение на основе данных из проекта рекомендаций 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
|
Например, чтобы изменить дозу ресвератрола, используемую для мыши (22,4 мг / кг), на дозу, основанную на BSA для крысы, умножьте 22,4 мг / кг на коэффициент Km для мыши, а затем разделите на коэффициент Km для крыса. Этот расчет дает эквивалентную дозу ресвератрола для крыс 11,2 мг / кг.
|
Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×
|
mouse Km(3)
|
= 11.2 mg/kg
|
|
rat Km(6)
|
Химическая информация
|
Molecular Weight (MW)
|
422.46
|
|
Formula
|
C21H18N4O4S
|
|
CAS No.
|
1276110-06-5
|
|
Storage
|
3 years -20℃Powder
|
|
6 months-80℃in solvent (DMSO, water, etc.)
|
|
Synonyms
|
N/A
|
|
Solubility (25°C) *
|
In vitro
|
DMSO
|
84 mg/mL
heating
(198.83 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.
|
|
Chemical Name
|
ethyl 6-(5-(phenylsulfonamido)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxylate
|
Калькулятор молярности Калькулятор разведения Калькулятор молекулярной массы
Группа Продуктов : PI3K / Akt / mTOR > Ингибитор PI3K
