CX-4945

CX-4945 : ATP competitive inhibitor of CSNK2A1

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe CX-4945 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

CSNK2A1

ATP competitive

More...

Probe Availability:

In Vitro Validations

Uniprot ID: P68400

Target Class: Kinase

Target SubClass: CMGC

Potency: Ki

Potency Value: 0.38 nM

Potency Assay: Binding assessed in Millipore Kinase Profiler assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Casein kinase II subunit alpha, CK2A1, CSNK2A1, CS ...

DOI Reference: 10.1158/0008-5472.CAN-10-1893

Uniprot ID: P68400

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 1 nM

Potency Assay: In vitro kinase assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Casein kinase II subunit alpha, CK2A1, CSNK2A1, CS ...

DOI Reference: 10.1158/0008-5472.CAN-10-1893

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 CK2 1 nM, DAPK3 17 nM, FLT3 35 nM, TBK1 35 nM, CLK3 41 nM, HIPK 45 nM, PIM1 46 nM, CDK1 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.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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.

(last updated: 27 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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

(last updated: 1 Jul 2016 )

Portal Comments

Grygier P. et al 2023 publication (DOI: 10.1021/acs.jmedchem.2c01887) shows that Silmitasertib is a dual inhibitor for DYRK1A and GSK3β kinases. "CX-4945 strongly binds to DYRK1A and GSK3β kinases with a dissociation constant (Kd) of 1.8 and 37.8 nM while being a very potent inhibitor of both kinases with IC50 in the nanomolar range (160 and 190 nM). Inhibitory activity toward both kinases was not only limited to in vitro assays but also extended to cellular models."

(last updated: 15 Mar 2023)