.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: 525.6 DTP3 es un inhibidor selectivo de GADD45β / MKK7, que inhibe la vía de supervivencia NF-κB selectiva del cáncer. \ n DTP3 interactúa físicamente con MKK7, tanto de forma aislada como dentro del complejo con GADD45β, y disocia el complejo GADD45β / MKK7 mediante un mecanismo alostérico. DTP3 destruye células selectivamente e induce apoptosis en células MM con MKK7 funcional y expresión elevada de GADD45β sin toxicidad para las células normales. Además, DTP3 muestra actividad sinérgica con bortezomib en dos líneas celulares MM diferentes, exhibiendo un índice de combinación de 0.21 en células U266 y de 0.56 en células KMS-12. \ n DTP3 (14,5 mg / kg / día) exhibe una potente actividad antitumoral contra MM en el modelo de plasmacitoma de ratón.
orte
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DTP3 Binding Assays
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The stoichiometry and KD value of the DTP3/MKK7 interaction are determined by tryptophan fluorescence quenching analysis, after fitting the fluorescence data with a nonlinear regression algorithm.
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Ensayo celular: [1]
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Cell lines
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CD138+ cells
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Concentrations
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~300 nM
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Incubation Time
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8 days
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Method
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[3H]Thymidine incorporation assays are performed using standard protocols. Briefly, cell lines are seeded into wells of 96-well plates at a concentration of 1.0x104 cells/well and then left untreated or treated daily with the indicated concentrations of peptides and maintained in complete RPMI-1640 medium at 37°C in 5% CO2, splitting them with medium as necessary. At 24, 72 or 144 hr, cells are incubated for an additional 16 hr with 0.037 MBq/well of [3H]thymidine, and then harvested onto glass fibre filter mats using a 96-well plate automated Tomtec cell harvester and analyzed by liquid scintillation spectroscopy with a LKB Wallac Trilux Microbeta 3-counter. Values are expressed as the percentage of the counts per minute (cpm) measured in the treated cultures relative to the cpm measured in the respective untreated cultures. The IC50 values are calculated using either 5 or 7 concentrations of compound and are defined as the mean concentration of compound inducing 50% inhibition of [3H]thymidine uptake relative to the uptake measured in untreated cells. Trypan blue exclusion assays are performed. Briefly, cells from lentivirus-infected cell lines are seeded into wells of 48-well plates in complete medium at a concentration of 2.0x105 cells/well, and then cultured at 37°C in 5% CO2, splitting them as necessary during the assays. Cell viability is monitored over a period of up to 8 days by cell counting using trypan blue, and the numbers of live infected cells in the cultures are extrapolated, where appropriate, from the cell counts by accounting for the percentages of eGFP+ cells, using flow cytometry. Values are expressed as the percentage of live infected cells present in thecultures at the times indicated relative to the number of live infected cells present in the same cultures at day 0.
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Estudio con animales: [1]
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Animal Models
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NOD/SCID mice bearing U266 or KMS-11 MM cells
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Formulation
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PBS
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Dosages
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14.5 mg/kg/day
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Administration
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Administered using Alzet osmotic pumps
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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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525.6
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Formula
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C26H35N7O5
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CAS No.
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no CAS
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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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100 mg/mL
(190.25 mM)
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Water
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100 mg/mL
(190.25 mM)
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Ethanol
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100 mg/mL
(190.25 mM)
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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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(R)-2-((R)-2-acetamido-3-(4-hydroxyphenyl)propanamido)-N-((R)-1-amino-1-oxo-3-phenylpropan-2-yl)-5-guanidinopentanamide
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : PI3K / Akt / mTOR > Inhibidor de Akt
