.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: \ n 425,42 Skepinone-L é um inibidor seletivo de p38α-MAPK com IC50 de 5 nM. \ n Atividade biológica Skepinone-L mostra inibição dependente da concentração da fosforilação de HSP27 (Ser82) através da via p38 MAPK com um IC50 celular de aproximadamente 25 nM, e também reduz as concentrações de TNF-α, IL-1β e IL-10, regulados por p38 MAPK, com IC50 variando de 30 a 50 nM. Skepinone-L (1 μM) anula a fosforilação do substrato p38 MAPK plaquetário Hsp27 ativado por estimulação com CRP, trombina ou tromboxano A2 análogo U-46619 e prejudica a secreção e agregação plaquetária. In vivo, a skepinona-L inibe a liberação de TNF-α induzida por Gal / LPS em 77%. Ensaio de cinase de protocolo (apenas para referência): [1]
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Cell-free p38α-MAPK activity assay
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Microtiter plates are coated with 50 μl of ATF-2 (10 μ/mL in TBS) for 1.5 h at 37 °C, washed with bidistilled water, blocked with blocking buffer (BB; 0.05% Tween 20, 0.25% BSA, 0,02% NaN3 in TBS) for 30 min at room temperature, and washed again. 50 μL of the respective test solution is incubated for 1 h at 37 °C. Test solutions contained 12 ng/well p38-MAPK diluted in kinase buffer (50 mM Tris, pH 7.5, 10 mM MgCl2, 10 mM β-glycerophosphate, 100 μg/mL BSA, 1 mM dithiothretiol, 0.1 mM Na3VO4, 100 μM rATP) with or without test substance (10 nM-100 μM). Test substances are dissolved in dimethyl sulfoxide to form stock solutions of 10 mM, all further dilution steps are carried out in kinase buffer. After subsequent washing, plates are blocked again with BB for 15 min followed by a washing step. 1. AB (50 μL, 1:500 in BB) was incubated for 1 h at 37 °C followed by washing and incubation with 50 μL of the 2. AB (alkaline phosphatase conjugated) (1:4000 in BB). After a final washing step, 100 μL of 4-nitrophenyl phosphate (NPP) is pipetted in each well and colour development was measured 1.5–2 h later with an enzyme-linked immunosorbent assay reader equipped with the SOFTmax PRO software at 405 nm.
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Estudo Animal: [1]
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Animal Models
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Mice
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Formulation
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Methyl cellulose
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Dosages
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~3 mg/kg
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Administration
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Oral administration
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Solubility
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0.5% methylcellulose,
30 mg/mL
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* 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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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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425.42
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Formula
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C24H21F2NO4
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CAS No.
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1221485-83-1
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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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85 mg/mL
(199.8 mM)
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Water
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<1 mg/mL
(
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Ethanol
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85 mg/mL
(199.8 mM)
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In vivo
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0.5% methylcellulose
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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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5H-Dibenzo[a,d]cyclohepten-5-one, 2-[(2,4-difluorophenyl)amino]-7-[(2R)-2,3-dihydroxypropoxy]-10,11-dihydro-
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Calculadora de molaridade Calculadora de diluição Calculadora de peso molecular
Grupo de Produto : MAPK > Inibidor de p38 MAPK
