XL413 (BMS-863233) 1169562-71-3
Descripción del producto
.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; relleno: 5px 0px 0px 5px;} \ n Peso molecular: \ n 326.18 XL413 (BMS-863233) es un inhibidor de quinasa homólogo (CDC7) del ciclo 7 de división celular potente y selectivo con IC50 de 3.4 nM, que muestra 63, 12 y Selectividad 35 veces mayor que CK2, Pim-1 y pMCM2, respectivamente. Fase 1/2. \ n Actividad biológica
Protocolo (solo como referencia) Ensayo de quinasa: [1]
Ensayo celular: [1]
Estudio con animales: [1]
Conversión de diferentes modelos de animales basados en BSA (valor basado en datos del Borrador de Directrices de la FDA)
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.
Información química
Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Description | 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 | Cdc7 [1] | Pim1 [1] | CK2 [1] | |||
IC50 | 3.4 nM | 42 nM | 212 nM | |||
In vitro | 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. | |||||
In vivo | 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. | |||||
Features |
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CDC7 kinase assay | 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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Cell lines | Colo-205 cells |
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Concentrations | ~10 μM |
Incubation Time | 24 hours |
Method | The cell proliferation is measured by BrdU incorporation assay, and viability is assayed by Cell Titer–Glo kits. |
Animal Models | Mice bearing Colo-205 xenografts |
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Formulation |
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Dosages | ~100 mg/kg |
Administration | p.o. |
Species | Baboon | Dog | Monkey | Rabbit | Guinea pig | Rat | Hamster | Mouse |
Weight (kg) | 12 | 10 | 3 | 1.8 | 0.4 | 0.15 | 0.08 | 0.02 |
Body Surface Area (m2) | 0.6 | 0.5 | 0.24 | 0.15 | 0.05 | 0.025 | 0.02 | 0.007 |
Km factor | 20 | 20 | 12 | 12 | 8 | 6 | 5 | 3 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
Rat dose (mg/kg) = mouse dose (22.4 mg/kg) × | mouse Km(3) | = 11.2 mg/kg |
rat Km(6) |
Molecular Weight (MW) | 326.18 |
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Formula |
C14H13Cl2N3O2 |
CAS No. | 1169562-71-3 |
Storage | 3 years -20℃Powder |
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6 months-80℃in solvent (DMSO, water, etc.) | |
Synonyms | N/A |
Solubility (25°C) * | In vitro | DMSO | <1 mg/mL ( |
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Water | 46 mg/mL heating (141.02 mM) | ||
Ethanol | <1 mg/mL ( | ||
* <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. |
Chemical Name | Benzofuro[3,2-d]pyrimidin-4(3H)-one, 8-chloro-2-(2S)-2-pyrrolidinyl-, hydrochloride |
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Grupos de Producto : Ciclo celular > Inhibidor de CDK
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