.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; padding: 5px 0px 0px 5px;} \ n Peso molecular: \ n 499,61 AZD9291 es un inhibidor de EGFR oral, irreversible y selectivo para mutantes con IC50 de 12,92, 11,44 y 493,8 nM para la deleción del exón 19 EGFR, L858R / T790M EGFR y WT EGFR, respectivamente. Fase 3. \ n Actividad biológica AZD9291 muestra una inhibición de la proliferación significativamente más potente en líneas celulares EGFR mutantes en comparación con las de tipo salvaje in vitro. AZD9291 (5 mg / kg po) provoca una regresión profunda de los tumores en los modelos de tumores EGFRm + (PC9) y EGFRm + / T790M (H1975) con una profunda inhibición de la fosforilación de EGFR y vías de señalización clave aguas abajo como AKT y ERK in vivo. Protocolo (solo como referencia) Ensayo de quinasa: [1]
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EGFR cellular phosphorylation assay
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Cells are seeded (10000 cells/well) in growth medium in Corning black, clear- bottomed 384-well plates and incubated at 37°C with 5% CO2 overnight. Cells are acoustically dosed using an Echo 555, with compounds serially diluted in 100% DMSO. Plates are incubated for a further 2h, then following aspiration of medium, 40μL lx lysis buffer is added to each well. Greiner black high bind 384-well plates are coated with capture antibody and then blocked with 3% BSA. Following removal of block, 15μL of lysate are transferred to the Greiner black high bind 384-well plates and incubated for 2 hours. Following aspiration and washing of the plates with PBS, 20μL, of detection antibody were added and incubated for 2 hours. Following aspiration and washing of the plates with PBS, 20μL of QuantaBlu fluorogenic peroxidase substrate are added and incubated for 1 hour. 20μL QuantaBlu stop solution are added to plates and fluorescence read on an Envision plate reader using Excitation 352nm wavelength and emission 460nm wavelength. The data obtained with each compound is exported into a suitable software package to perform curve fitting analysis. From this data an IC50 value is determined by calculation of the concentration of compound that is required to give a 50% effect.
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Estudio con animales: [2]
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Animal Models
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Mice bearing PC9 and H1975 xenograft tumors
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Formulation
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Dosages
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~5 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)
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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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Información química
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Molecular Weight (MW)
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499.61
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Formula
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C28 H33 N7 O2
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CAS No.
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1421373-65-0
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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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99 mg/mL
heating
(198.15 mM)
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Water
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<1 mg/mL
(
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Ethanol
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43 mg/mL
heating
(86.06 mM)
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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-Propenamide, N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : Proteína tirosina quinasa > Inhibidor de EGFR
