.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: 262.69 VU 0361737 es un modulador alostérico positivo selectivo (PAM) para el receptor mGlu4 con EC50 de 240 nM y 110 nM en los receptores humanos y de rata, respectivamente, muestra una actividad débil en mGlu5 y Los receptores mGlu8, están inactivos en los receptores mGlu1, mGlu2, mGlu3, mGlu6 y mGlu7, pueden penetrar en el SNC. \ n Actividad biológica VU0361737 está inactiva en los receptores mGlu1, mGlu2, mGlu3, mGlu6 y mGlu7 y muestra una actividad débil en los receptores mGlu8 y mGlu5. VU0361737 muestra un CL alto in vivo en ratas, una vida media corta (T1 / 2 20 min) y demuestra una exposición cerebral significativa (relación cerebro-plasma de 4,1). \ n Protocolo (solo como referencia) Ensayo de quinasa: [2]
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Calcium mobilization assays
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Human mGluR4/Gqi5/CHO cells (30,000 cells/20 •l/well) are plated in blackwalled, clear-bottomed, TC treated, 384 well plates in DMEM containing 10% dialyzed FBS, 20 mM HEPES, 100 units/ml penicillin/streptomycin, and 1 mM sodium pyruvate. The cells are grown overnight at 37 °C in the presence of 5% CO2. During the day of assay, the medium is replaced with 20 μL of 1 μM Fluo-4, AM prepared as a 2.3 mM stock in DMSO and mixed in a 1:1 ratio with 10% (w/v) pluronic acid F-127 and diluted in Assay Buffer (Hank`s balanced salt solution, 20 mM HEPES and 2.5 mM Probenecid) for 45 minutes at 37 °C. Dye is removed and replaced with 20 μL of Assay Buffer. Test compounds are transferred to daughter plates using an Echo acoustic plate reformatter and then diluted into Assay Buffer. Ca2+ flux is measured using the Functional Drug Screening System 6000. Baseline readings are taken (10 images at 1 Hz, excitation, 470±20 nm, emission, 540±30 nm) and then 20 •l/well test compounds are added using the FDSS`s integrated pipettor. Cells are incubated with compounds for approximately 2.5 minutes and then an EC20 concentration of glutamate is applied; 2 minutes later an EC80 concentration of glutamate is added. For concentration-response
curve experiments, compounds are serially diluted 1:3 into 10 point concentration response curves and are transferred to daughter plates using the Echo. Test compounds are again applied and followed by EC20 concentrations of glutamate. For fold shift experiments, compounds are added at 2X their final concentration and then increasing concentrations of glutamate are added in the presence of vehicle or the appropriate concentration of test compound. Curves are fitted using a four point logistical equation using Microsoft XLfit. Subsequent confirmations of concentrationresponse
parameters are performed using independent serial dilutions of source compounds and data from multiple days experiments are integrated and fit using a four point logistical equation in GraphPad Prism. Calcium assays are used to assess activity of compounds at mGluRs 1, 4 and 5.
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Estudio con animales: [1]
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Animal Models
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Sprague-Dawley rats
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Formulation
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10% Tween-80
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Dosages
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10 mg/kg
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Administration
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ip
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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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262.69
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Formula
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C13H11ClN2O2
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CAS No.
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1161205-04-4
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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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53 mg/mL
(201.75 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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2-Pyridinecarboxamide, N-(4-chloro-3-methoxyphenyl)-
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : Señalización neuronal > Inhibidor de GluR
