.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: 257.27 AS-605240 inhibe selectivamente PI3Kγ con IC50 de 8 nM, más de 30 veces y 7.5 veces más selectivo para PI3Kγ que PI3Kδ / β y PI3Kα, respectivamente. \ n AS-605240 es un inhibidor de PI3Kγ competitivo con ATP, con valores de Ki de 7,8 nM. AS-605240 es selectivo de isoformas, ya que AS-605240 también inhibe PI3Kα, β y δ, con IC50 de 60, 270 y 300 nM, respectivamente. AS-605240 inhibe la fosforilación de PKB mediada por C5a con IC50 de 90 nM. En los monocitos derivados de la médula ósea (BMDM), AS-605240 (1 μM) bloquea la fosforilación de PKB inducida por MCP-1- o CSF-1. En las sinapsis de SC-CA1 en ratones, AS-605240 (100 nM) elimina NMDAR LTD, sin afectar a mGluR LTD, despotenciación y LTP. \ n En el modelo de peritonitis de ratón inducido por RANTES, AS-605240 reduce la quimiotaxis de neutrófilos con una DE50 de 9,1 mg / kg. En una artritis inducida por αCII, AS-605240 (50 mg / kg) protege contra el síntoma αCII-IA. En un modelo de ratón de artritis inducida por colágeno, AS-605240 (50 mg / kg) también suprime la inflamación y el daño articular. En un modelo de diabetes inducida por obesidad (ratones ob / ob), AS-605240 (10 mg / kg) reduce los niveles de glucosa en sangre, mejora significativamente tanto la sensibilidad a la insulina como la tolerancia a la glucosa sin afectar el peso corporal. AS-605240 (30 mg / kg) muestra efectos más profundos con un aumento de peso ligeramente menor. Además, AS-605240 reduce la abundancia de cajeros automáticos y los niveles circulantes de MCP-1.
orte
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In vitro PI3K lipid kinase assay
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(1) For PI3Kγ: human PI3Kγ (100 ng) is incubated at RT with kinase buffer (10 mM MgCl2, 1 mM β-glycerophosphate, 1 mM DTT, 0.1 mM Na3VO4, 0.1% Na Cholate and 15 μM ATP/100 nCi γ[33P]ATP, final concentrations) and lipid vesicles containing 18 μM PtdIns and 250 μM of PtdSer (final concentrations), in the presence of AS-605240 or DMSO. Kinase reaction is stopped by adding 250 μg of Neomycin-coated Scintillation Proximity Assay (SPA) beads. (2) For PI3Kα, β, and δ: varying amounts of ATP are incubated with the different purified PI3K isoforms and saturating concentrations of PtdIns. Consequently, IC50 determinations with PI3Kα, β, and δ, to evaluate inhibitor selectivity are performed as follows: 60 ng of PI3Kα are incubated at RT with kinase buffer, as described for PI3Kγ (but containing 89 μM ATP/300 nCi γ[33P]ATP and no Na Cholate, instead) and lipid vesicles containing 212 μM PtdIns and 58 μM of PtdSer. 100 ng of PI3Kβ are incubated at RT with kinase buffer (containing 70 μM ATP/300 nCi γ[33P]ATP, 4 mM MgCl2 and no Na Cholate) and lipid vesicles containing 225 μM PtdIns and 45 μM of PtdSer. 90 ng of PI3Kδ are incubated with kinase buffer (containing 65 μM ATP/300 nCi γ[33P]ATP, 1 mM MgCl2, and no Na Cholate) and lipid vesicles containing 100 μM PtdIns and 170 μM of PtdSer. The reactions are stopped after 2 hours.
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Ensayo celular: [1]
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Cell lines
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RAW264 macrophages
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Concentrations
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1 nM - 10 μM, dissolved in DMSO
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Incubation Time
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30 min
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Method
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After a 3-hour starvation in serum-free medium, Cells are pretreated with AS-605240 or DMSO for 30 min and stimulated for 5 min with 50 nM of C5a. PKB phosphorylation is monitored using phosphorylated Ser473 Akt-specific antibody and standard ELISA protocols.
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Estudio con animales: [1]
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Animal Models
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RANTES-induced mouse model of peritonitis (female Balb/C or C3H), αCII-induced mouse model of arthritis, and collagen-induced mouse model of arthritis (CIA) (male DBA/1)
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Formulation
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Dissolved in 0.5% carboxymethylcellulose/0.25% Tween-20
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Dosages
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50 mg/kg
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Administration
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Orally
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Solubility
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0.5% CMC/0.25% Tween 80,
11 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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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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257.27
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Formula
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C12H7N3O2S
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CAS No.
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648450-29-7
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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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0.4 mg/mL
(1.55 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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0.5% CMC/0.25% Tween 80
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11 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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(Z)-5-(quinoxalin-6-ylmethylene)thiazolidine-2,4-dione
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : PI3K / Akt / mTOR > Inhibidor de PI3K
