.cp_wz table {border-top: 1px solid #ccc; border-left: 1px solid #ccc; } .cp_wz table td {border-right: 1px solid #ccc; borda inferior: 1px sólido #ccc; preenchimento: 5px 0px 0px 5px;} .cp_wz tabela th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; preenchimento: 5px 0px 0px 5px;} \ n Peso molecular: \ n 326,18 XL413 (BMS-863233) é um inibidor de quinase homólogo (CDC7) do ciclo 7 de divisão celular potente e seletivo com IC50 de 3,4 nM, mostrando 63-, 12- e Seletividade de 35 vezes sobre CK2, Pim-1 e pMCM2, respectivamente. Fase 1/2. \ n Atividade biológica
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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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Ensaio de cinase de protocolo (apenas para referência): [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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Ensaio de células: [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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Estudo Animal: [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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Conversão de diferentes modelos de animais com base em BSA (valor com base em dados das diretrizes preliminares da 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 exemplo, para modificar a dose de resveratrol usada para um camundongo (22,4 mg / kg) para uma dose baseada na BSA para um rato, multiplique 22,4 mg / kg pelo fator Km para um camundongo e, em seguida, divida pelo fator Km para um rato. Este cálculo resulta em uma dose equivalente de rato para o 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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Informação Química
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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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Calculadora de molaridade Calculadora de diluição Calculadora de peso molecular
Grupo de Produto : Ciclo de célula > Inibidor CDK
