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Molekulargewicht:
525,6 DTP3 ist ein selektiver GADD45β/MKK7-Inhibitor, der den krebsselektiven NF-κB-Überlebensweg hemmt.
Biologische Aktivität DTP3 interagiert physikalisch mit MKK7, sowohl isoliert als auch innerhalb des Komplexes mit GADD45β, und dissoziiert den GADD45β/MKK7-Komplex über einen allosterischen Mechanismus. DTP3 tötet selektiv Zellen und induziert Apoptose in MM-Zellen mit funktionellem MKK7 und erhöhter GADD45β-Expression ohne Toxizität für normale Zellen. Darüber hinaus zeigt DTP3 eine synergistische Aktivität mit Bortezomib in zwei verschiedenen MM-Zelllinien mit einem Kombinationsindex von 0,21 in U266-Zellen und von 0,56 in KMS-12-Zellen. DTP3 (14,5 mg/kg/Tag) zeigt eine starke Antitumoraktivität gegen MM im Mausplasmozytommodell. Protokoll (nur als Referenz) Kinase-Assay: [1]
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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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Zellassay: [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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Tierstudie: [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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Umrechnung verschiedener Modelltiere basierend auf BSA (Wert basierend auf Daten aus FDA Draft Guidelines)
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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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Um beispielsweise die Resveratrol-Dosis für eine Maus (22,4 mg/kg) auf eine Dosis basierend auf dem BSA für eine Ratte zu ändern, multiplizieren Sie 22,4 mg/kg mit dem Km-Faktor für eine Maus und dividieren Sie dann durch den Km-Faktor für eine Ratte. Diese Berechnung ergibt eine Ratten-Äquivalentdosis für Resveratrol von 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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Chemische Informationen
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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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Molaritätsrechner Verdünnungsrechner Molekulargewichtsrechner
Produktgruppe : MAPK > JNK-Inhibitor
