.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: 409.61 PHT-427 es un inhibidor dual de Akt y PDPK1 (unión de alta afinidad para los dominios PH de Akt y PDPK1) con Ki de 2.7 μM y 5.2 μM, respectivamente. \ n PH-427 es un inhibidor del dominio de homología de pleckstrina para Akt / PDPK1. PH-427 reduce significativamente fosfo-Ser241-PDPK1 fosfo-Thr308-Akt en células de cáncer de próstata PC-3 a 10 μM, lo que muestra que PHT-427 podría inhibir tanto Akt como PDPK1. PHT-427 también inhibe la translocación de los dominios PH Akt y PDPK1 en la membrana plasmática. PHT-427 induce la apoptosis e inhibe la fosforilación de AKT con IC50 de 8,6 μM (en células BxPC-3), que principalmente en su residuo Ser473 y menos fuertemente en el residuo Thr308 sin afectar la expresión de la proteína Akt total. PHT-427 también muestra antiproliferación en células Panc-1 con IC50 de 65 µM. \ n PHT-427 muestra una gran actividad antitumoral en xenoinjertos de cáncer de páncreas BxPC-3, de mama MCF-7 y de cáncer de NSCL A-549. PHT-427 proporciona hasta un 80% de inhibición del crecimiento tumoral en BxPC-3 a dosis de 125 a 250 mg / kg.
orte
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Surface plasmon resonance (SPR) spectroscopy binding assays
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All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacore's Amine Coupling Kit to a level of 10,000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10 × the predicted KD are injected at a high flow rate (30μL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less.
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Ensayo celular: [2]
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Cell lines
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Panc-1 cells
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Concentrations
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1-50 μM
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Incubation Time
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|
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Method
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Cell growth inhibition is determined using a micro-cytoxicity assay. Cells are plated in 96-well micro-cytoxicity at 5-10 × 103 cells per well (depending on cell doubling time) and grown for 7 days. PHT-427 dissolved in DMSO is added directly to the media, at various concentrations ranging from 1 to 50 μM. The endpoint is spectrophotometric determination of the protein content of each well using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. A concentration-response relationship at two or more concentration levels is used to obtain an IC50 for PHT-427.
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Estudio con animales: [1]
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Animal Models
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BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells are injected subcutaneously into the flanks of female scid mice.
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Formulation
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40 to 50 mg/mL in sesame seed oil
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Dosages
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125-250 mg/kg
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Administration
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Oral administration
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Solubility
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5% DMSO/95% Corn oil,
5 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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\ n Información química
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Molecular Weight (MW)
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409.61
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Formula
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C20H31N3O2S2
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CAS No.
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1191951-57-1
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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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CS-0223
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Solubility (25°C) *
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In vitro
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DMSO
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82 mg/mL
(200.19 mM)
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Water
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<1 mg/mL
(
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Ethanol
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60 mg/mL
(146.48 mM)
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In vivo
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5% DMSO/95% Corn oil
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5 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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4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : PI3K / Akt / mTOR > Inhibidor de Akt
