WZ4003

Reagent Authentication Certificate:

Chemical Probes Portal WZ4003.pdf

Protein target name:

NUAK1, NUAK2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

Up to 1 uM

Probe Availability

MedChem Express (1214265-58-3)

Abcam (1214265-58-3)

Tocris (1214265-58-3)

Cayman (1214265-58-3)

MilliporeSigma (1214265-58-3)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CAMK

HUGO ID:

HGNC:14311 HGNC:29558

Entrez gene ID:

9891 81788

UNIPROT ID:

O60285 Q9H093

Target alias:

ARK5, SNARK

Probe Details

Chemical Probes Portal ID:

CPP103

Probe alias:

WZ-4003, WZ 4003

PubChem CID:

72200024

SMILES string:

CCC(=O)NC1=CC(=CC=C1)OC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCN(CC4)C)OC

InChi Key:

SDGJBAUIGHSMRI-UHFFFAOYSA-N

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

20 nM (NUAK1) 100 nM (NUAK2)

Off target activity

Potency assay (off target):

No significant off-target activity was detected against 140 additional protein kinases at 1 uM.

In cell validation

On target activity in cells

Potency assay (cells):

In HEK-293 cells, WZ4003 dose-dependently inhibited NUAK protein substrate phosphorylation.

Target engagement assay (cells):

Indirect: inhibition of protein substrate phosphorylation, and in cells expressing the resistant mutant NUAK1 A195, WZ4003 did not inhibit protein substrate phosphorylation at 30 uM.

Off target activity in cells

Potency assay, off target (cells):

In HEK-293 cells, WZ4003 did not inhibit phosphorylation of AMPK substrates.

Primary Reference

Reference (doi):

10.1042/BJ20131152

Reference (PMID):

24171924

External Resources

Available data:

GDSC2

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

The compound has good kinase selectivity, but the cellular activity is not at the level I would consider useful for a bona fide probe (<1 uM). The authors have highlighted a few more potent compounds that could be used in parallel. They suffer from a worse kinome profile. This compound has excellent kinase selectivity but is only weekly active in cells.

Jun 16 2016 - 5:59pm

This appears to be a highly selective NUAK1 inhibitor without significant off-target actions at 140 other tested kinases. There are no data available for potential off-target actions at other druggable targets (e.g., GPCRs, ion channels and so on).

Jun 29 2016 - 7:46pm

No available PK or toxicology data; no way to judge whether or not it should be utilized in vivo. The probe is selective and has a target not well addressed by other molecules. Further work on physiochemistry, pharmacokinetics, and toxicology scouting could prove the probe useful (or disqualify for further use).

Jun 30 2016 - 4:52am

WZ4003

Probe Availability

Probe Information

Target Details

ARK5, SNARK

Probe Details

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

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WZ4003

Probe Availability

Probe Information

Target Details

ARK5, SNARK

Probe Details

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?