XL413 (BMS-863233)

Catalog No.S7547

XL413 (BMS-863233) Chemical Structure

Molecular Weight(MW): 326.18

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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1 Customer Review

  • Effects of XL413 plus pirfenidone on 10T1/2 cells morphology, proliferation and TGF-β1-induced α-SMA expression. Cells were exposed to control, XL413 (10 μM), pirfenidone (1 mg/ml) or XL413 plus pirfenidone. (G) Laser confocal scanning was used for visualization of α-SMA protein expression and cellular morphological changes.

    Exp Cell Res, 2015, 339(2):289-99.. XL413 (BMS-863233) purchased from Selleck.

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Biological Activity

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.
Targets
Cdc7 [1] Pim1 [1] CK2 [1]
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. [1]

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. [1]

Protocol

Kinase Assay:[1]
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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.
Cell Research:[1]
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  • Cell lines: Colo-205 cells
  • 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.
    (Only for Reference)

Solubility (25°C)

In vitro Water 46 mg/mL warmed (141.02 mM)
DMSO <1 mg/mL
Ethanol <1 mg/mL
In vivo

* 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 Information

Molecular Weight 326.18
Formula

C14H13Cl2N3O2

CAS No. 1169562-71-3
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00838890 Terminated Refractory Hematologic Cancer Bristol-Myers Squibb|Exelixis March 2009 Phase 1|Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID