.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: 368.41 VE-821 es un inhibidor competitivo de ATP potente y selectivo de ATR con Ki / IC50 de 13 nM / 26 nM, muestra inhibición de la fosforilación de H2AX, actividad mínima contra ATM de PIKK, DNA-PK, mTOR y PI3Kγ. \ N VE-821 muestra una excelente selectividad para ATR con una mínima reactividad cruzada contra los PIKK relacionados ATM, DNA-PK, mTOR y PI3K (Kis de 16 μM, 2,2 μM,> 1 μM y 3,9 μM, respectivamente. VE-821 por sí solo provoca la muerte de una gran fracción de las poblaciones de células cancerosas, pero solo limita de manera reversible la progresión del ciclo celular en las células normales, con una muerte mínima o efectos perjudiciales a largo plazo. VE-821 junto con el tratamiento con cisplatino muestra la sinergia más marcada. VE-821 inhibe el crecimiento de células H2AX con IC50 de 800 nM. \ n Protocolo (solo como referencia) Ensayo de quinasa: [2]
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Kinase inhibition
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The ability of compounds to inhibit ATR, ATM or DNAPK kinase activity istested using a radiometric-phosphate incorporation assay. A stock solution isprepared consisting of the appropriate buffer, kinase, and target peptide. To this isadded the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [γ-33P]ATP solution and incubated at 25 ℃. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared as per manufacturer's instructions, and washed six times with 200 μL of 100 mM phosphoric acid, prior to the addition of 100 μL of scintillation cocktail and scintillation counting on a 1450 Microbeta Liquid Scintillation Counter. Dose−response data are analyzed using GraphPad Prism software
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Ensayo celular: [2]
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Cell lines
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H2AX cells
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Concentrations
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Incubation Time
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96 hours
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Method
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Cells are plated in 96-well plates and allowed to adhere overnight. The following day, compounds are added at the indicated concentrations in a final volume of 200μL, and the cells are then incubated for 96 h. MTS reagent (40μL) isthen added, and 1 h later, absorbance at 490 nm ismeasured using a SpectraMax Plus 384 plate reader. Synergy and antagonism are assessed using Macsynergy software.
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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)
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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 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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\ n Información química
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Molecular Weight (MW)
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368.41
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Formula
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C18H16N4O3S
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CAS No.
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1232410-49-9
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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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Solubility (25°C) *
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In vitro
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DMSO
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74 mg/mL
(200.86 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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In vivo
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30% PEG400/0.5% Tween80/5% propylene glycol
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30 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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2-Pyrazinecarboxamide, 3-amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : PI3K / Akt / mTOR > Inhibidor ATM / ATR
