.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: 368,41 VE-821 é um potente e seletivo inibidor competitivo de ATP de ATR com Ki / IC50 de 13 nM / 26 nM, mostra inibição da fosforilação de H2AX, atividade mínima contra PIKKs ATM, DNA-PK, mTOR e PI3Kγ. \ N VE-821 mostra excelente seletividade para ATR com reatividade cruzada mínima contra os PIKKs relacionados ATM, DNA-PK, mTOR e PI3K (Kis de 16 μM, 2,2 μM,> 1 μM e 3,9 μM, respectivamente. VE-821 sozinho comete uma grande fração de populações de células cancerosas à morte, mas apenas limita reversivelmente a progressão do ciclo celular em células normais, com morte mínima ou efeitos prejudiciais a longo prazo. VE-821 juntamente com tratamento com cisplatina mostra o sinergia mais marcada. VE-821 inibe o crescimento de células H2AX com IC50 de 800 nM. \ n Protocolo (apenas para referência) Ensaio de quinase: [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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Ensaio de células: [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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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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\ n Informação 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 molaridade Calculadora de diluição Calculadora de peso molecular
Grupo de Produto : PI3K / Akt / mTOR > Inibidor ATM / ATR
