Home Cell Cycle CDK inhibitor XL413

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XL413 CDK inhibitor

Cat.No.S7547

XL413 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.
XL413 CDK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 326.18

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Quality Control

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human MDA-MB-231T cells Function assay 4 h Inhibition of CDC7 in human MDA-MB-231T cells assessed as inhibition of MCM2 phosphorylation at Ser53 after 4 hrs, IC50=0.118 μM 22560567
human Caco2 cells Function assay 4 h Inhibition of CDC7 in human Caco2 cells assessed as inhibition of MCM2 phosphorylation at Ser53 after 4 hrs, IC50=0.14 μM 22560567
human Caco2 cells Proliferation assay Antiproliferative activity against human Caco2 cells assessed as inhibition of anchorage-independent growth in soft agar, IC50=0.715 μM 22560567
Caco2 cells Function assay Induction of apoptosis in human Caco2 cells assessed as increase in caspase 3/7 activity, EC50=2.288 μM 22560567
MDA-MB-468 Function assay Inhibition of PHGDH in human MDA-MB-468 cells assessed as decrease in serine flux, EC50 = 2.3 μM. 29555419
MDA-MB-468 Cytotoxicity assay Cytotoxicity against human MDA-MB-468 cells, EC50 = 8 μM. 29555419
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 326.18 Formula

C14H13Cl2N3O2

 Storage (From the date of receipt)
CAS No. 1169562-71-3 Download SDF Storage of Stock Solutions

Synonyms BMS-863233 Smiles C1CC(NC1)C2=NC3=C(C(=O)N2)OC4=C3C=C(C=C4)Cl.Cl

Solubility

In vitro
Batch:

Water : 46 mg/mL

DMSO : Insoluble
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Working concentration: mg/ml;

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC50/Ki
Cdc7 [1]
(Cell-free assay)
3.4 nM
Pim1 [1]
(Cell-free assay)
42 nM
CK2 [1]
(Cell-free assay)
212 nM
In vitro
In MDA-MB-231T and Colo-205 cell lines, XL413 results in inhibition of CDC7 specific phosphorylation of MCM2. This compound also inhibits the cell proliferation, decreases cell viability and elicits the caspase 3/7 activity in Colo-205 cells. Moreover, it results in modified S phase progression that subsequently leads to apoptotic cell death. [1]
Kinase Assay
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.
In vivo
In a Colo-205 xenograft model, XL413, at the 3 mg/kg dose, causes 70% inhibition of phosphorylated MCM2, and this compound causes significant tumor growth regression at the 100 mg/kg dose. [1]
References

Applications

Methods Biomarkers Images PMID
Western blot p-Mcm2 / Mcm2 S7547-WB1 25412417

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00886782 Terminated
Advanced Solid Cancers|Metastatic Cancer
Bristol-Myers Squibb|Exelixis
 May 31 2009 Phase 1|Phase 2
NCT00838890 Terminated
Refractory Hematologic Cancer
Bristol-Myers Squibb|Exelixis
 March 2009 Phase 1|Phase 2

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