.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: 450,92 Suvorexant (MK-4305) es un potente antagonista del receptor de OX dual con Ki de 0,55 nM y 0,35 nM para el receptor OX1 y el receptor OX2, respectivamente. Fase 3. \ n Suvorexant tiene una excelente permeabilidad pasiva y biodisponibilidad oral, e induce efectos favorables del sueño en ratas. Además, el suvorexant reduce de manera significativa y dependiente de la dosis la actividad locomotora y promueve el sueño en ratas (10, 30 y 100 mg / kg), perros (1 y 3 mg / kg) y monos rhesus (10 mg / kg). \ n Protocolo (solo como referencia) Ensayo de quinasa: [1]
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FLIPR Assay
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For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the Ile408-Val variant of the orexin 1 receptor or the human orexin 2 receptor, are grown in Iscove`s modified DMEM containing 2 mM l-glutamine, 0.5 g/mL G418, 1% hypoxanthine-thymidine supplement, 100 U/mL penicillin, 100 ug/mL streptomycin, and 10% heat-inactivated fetal calf serum. The cells are seeded at 20000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-d-lysine. All reagents are from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37 °C and 6% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 0.5 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES and 2.5 mM probenecid, pH 7.4) for use in the assay at a final concentration of 0.3−2 nM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted and pipetted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed three times with 100 μL assay buffer and then incubated for 60 min (37 °C, 6% CO2) in 60 μL of assay buffer containing 1 μM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells washed three times with 100 μL of assay buffer. Then 30 μL of that same buffer is left in each well. Within the fluorescent imaging plate reader, test compounds are added to the plate in a volume of 15 μL, incubated for 5 min, and finally 15 μL of agonist is added. Fluorescence is measured for each well at 1 s intervals for 1 min and at 6 s intervals for 4 min, and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 0.3−2 nM Ala-6,12 orexin-A with buffer in place of antagonist. For each antagonist, the IC50 value (the concentration of compound needed to inhibit 50% of the agonist response) is determined.
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Estudio con animales: [1]
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Animal Models
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Adult male Sprague−Dawley rats
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Formulation
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20% aqueous solution of TPGS
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Dosages
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~10 mg/kg
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Administration
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Oral gavage
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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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450.92
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Formula
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C23H23ClN6O2
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CAS No.
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1030377-33-3
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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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10 mg/mL
(22.17 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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Chemical Name
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5-Chloro-2-[(5R)-5-methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl]-1,3-benzoxazole
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orte
Grupos de Producto : Señalización neuronal > Inhibidor del receptor de OX
