CX-4945

Protein target name:

CSNK2A1

Mechanism of action:

ATP-competitive inhbitor

Recommended Concentration for use in cells:

N/A

Probe Availability

MedChem Express (1009820-21-6)

Abcam (1009820-21-6)

Cayman (1009820-21-6)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:2457

Entrez gene ID:

1457

UNIPROT ID:

P68400

Target alias:

CK2A1, CKII, CSNK2A3, CK2, casein kinase 2

Probe Details

Chemical Probes Portal ID:

CPP128

Probe alias:

Silmitasertib

PubChem CID:

24748573

ChEMBL ID:

CHEMBL1230165

SMILES string:

C1=CC(=CC(=C1)Cl)NC2=C3C=CN=CC3=C4C=CC(=CC4=N2)C(=O)O

InChi Key:

MUOKSQABCJCOPU-UHFFFAOYSA-N

Orthogonal probe:

SGC-CK2-1

PAINs evaluation:

PAINs free

Physico-chemical properties

Solubility - preferred solvent:

DMSO

Solubility - concentration:

5 mM

Storage Recommendations

Storage (solution):

-70 oC

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.38 nM

Potency assay:

Binding assessed in Millipore Kinase Profiler assay, and activity assessed in in vitro kinase assay: IC50 = 1 nM

Off target activity

Potency (off target):

IC50

Off target protein and potency:

CK2 1 nMDAPK3 17 nMFLT3 35 nMTBK1 35 nMCLK3 41 nMHIPK 45 nMPIM1 46 nMCDK1 56 nM

Potency assay (off target):

CX-4945 was tested against 285 kinases in Millipore Kinase Profiler, and in vitro kinase assays. In the latter, only 7/238 kinases were inhibited by >90% at 50 nM.

In cell validation

On target activity in cells

Potency assay (cells):

CX-4945 dose-dependently inhibited substrate phosphorylation in BT-474, BxPC-C and HUVEC cells. CX-4945 inhibited phosphorylation of AKT at S129.

Target engagement assay (cells):

Indirect: inhibition of substrate phosphorylation

In vivo validation

Organism:

CrTac:Ncr-Foxn1^nu miceNu/nu mice

Dose:

75 mg/mL

Route of delivery:

Oral

Systemic clearance:

2.7 L/kg/hr

Cmax:

15 uM

Tmax:

0.25 hr

Organ of Interest

Organ (O):

xenograft

Target engagement assay:

Indirect: immunohistochemistry showed inhibition of protein substrate phosphorylation in xenograft tumor tissue (phosphorylation of p21 at T145).

Primary Reference

Reference (doi):

10.1158/0008-5472.CAN-10-1893 10.1038/leu.2013.232 10.1007/s11010-011-0956-5

Reference (PMID):

21159648 21755459

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

CX-4945 also inhibits DAPK3, FLT3, TBK1, CLK3, HIPK3, PIM1, and CDK1/cyclin B <56 nM; it was shown to be more selective for CK2 in functional cellular assays at 10 uM. CX-4945 exhibits a T1/2 10-14 h in rats and and F (%) 80.

Jun 30 2016 - 12:33am

CX-4945 is a highly potent inhibitor of CLKs (IC50 range ~ 4-90 nM, top target CLK2 with an IC50 of 3.8 nM), and it therefore exerts a strong and profound effect on pre-mRNA splicing in a CK2-independent manner which should be considered when interpreting results obtained with this compound.

Jun 30 2016 - 6:33pm

CX-4945 should be used with caution due to significant off-target activity; appropriate control experiments should be included.

Jul 3 2016 - 3:47pm

CX-4945

Probe Availability

Probe Information

Target Details

CK2A1, CKII, CSNK2A3, CK2, casein kinase 2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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CX-4945

Probe Availability

Probe Information

Target Details

CK2A1, CKII, CSNK2A3, CK2, casein kinase 2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?