product name XL413 (BMS-863233)
Description: XL413 (BMS-863233) is a novel, highly potent and selective cell division cycle 7 homolog (CDC7) kinase inhibitor with IC50 of 3.4 nM, it shows 63-, 12- and 35-fold selectivity over CK2, Pim-1 and pMCM2, respectively. 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.
References: Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31.
326.18
Formula
C14H13Cl2N3O2
CAS No.
1169562-71-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: <1 mg/mL
Water: 46 mg/mL (141.02 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19405909
| In Vitro |
In vitro activity: 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. 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 Assay: The cell proliferation is measured by BrdU incorporation assay, and viability is assayed by Cell Titer–Glo kits. Celllin used: Colo-205 cells. |
|---|---|
| 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. |
| Animal model | |
| Formulation & Dosage | |
| References | Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31. |
