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Molekulargewicht:
326,18 XL413 (BMS-863233) ist ein potenter und selektiver Zellteilungszyklus-7-Homolog (CDC7)-Kinase-Inhibitor mit IC50 von 3,4 nM, der 63-, 12- und zeigt 35-fache Selektivität gegenüber CK2, Pim-1 bzw. pMCM2. Phase 1/2.
Biologische Aktivität
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Description
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XL413 (BMS-863233) is a potent and selective cell division cycle 7 homolog (CDC7) kinase inhibitor with IC50 of 3.4 nM, showing 63-, 12- and 35-fold selectivity over CK2, Pim-1 and pMCM2, respectively. Phase 1/2.
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Targets
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Cdc7 [1]
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Pim1 [1]
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CK2 [1]
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IC50
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3.4 nM
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42 nM
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212 nM
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In vitro
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In MDA-MB-231T and Colo-205 cell lines, XL413 results in inhibition of CDC7 specific phosphorylation of MCM2. XL413 also inhibits the cell proliferation, decreases cell viability and elicits the caspase 3/7 activity in Colo-205 cells. Moreover, XL413 results in modified S phase progression that subsequently leads to apoptotic cell death.
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In vivo
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In a Colo-205 xenograft model, XL413, at the 3 mg/kg dose, causes 70% inhibition of phosphorylated MCM2, and causes significant tumor growth regression at the 100 mg/kg dose.
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Features
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Protokoll (nur als Referenz) Kinase-Assay: [1]
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CDC7 kinase assay
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Kinase activity and compound inhibition are determined using the luciferase-luciferin-coupled chemiluminescence assay and measured as the percentage of ATP utilized following the kinase reaction in a 384-well format. The final CDC7 kinase assay condition is 6 nM CDC7/ASK, 1 μM ATP, 50 mM Hepes pH 7.4, 10 mM MgCl2, 0.02% BSA, 0.02% brij 35, 0.02% tween 20 and 1 mM DTT. It is worthy to note that the CDC7/ASK protein exhibits substrate-independent ATP utilization. All kinase reactions are incubated at room temperature for 1-2 h.
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Zellassay: [1]
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Cell lines
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Colo-205 cells
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Concentrations
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~10 μM
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Incubation Time
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24 hours
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Method
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The cell proliferation is measured by BrdU incorporation assay, and viability is assayed by Cell Titer–Glo kits.
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Tierstudie: [1]
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Animal Models
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Mice bearing Colo-205 xenografts
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Formulation
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Dosages
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~100 mg/kg
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Administration
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p.o.
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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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326.18
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Formula
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C14H13Cl2N3O2
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CAS No.
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1169562-71-3
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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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<1 mg/mL
(
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Water
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46 mg/mL
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(141.02 mM)
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Ethanol
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<1 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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Benzofuro[3,2-d]pyrimidin-4(3H)-one, 8-chloro-2-(2S)-2-pyrrolidinyl-, hydrochloride
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Molaritätsrechner Verdünnungsrechner Molekulargewichtsrechner
Produktgruppe : Zellzyklus > CDK-Inhibitor
