WZ4003

Inhibitor of NUAK1, NUAK2

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(1 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.

Information

NUAK1
NUAK2

Inhibitor

DOI - 10.1042/BJ20131152

Probe Availability:

In Vitro Validations

Uniprot ID: O60285

Target Class: Kinase

Target SubClass: CAMK

Potency: IC 50

Potency Value: 20 nM

Potency Assay: Kinase assay

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

Target aliases:

NUAK family SNF1-like kinase 1, OMPHK1, KIAA0537, ...

DOI Reference: 10.1042/BJ20131152

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): No significant off-target activity was detected against 140 additional protein kinases at 1 uM.

Probe Selectivity in Vitro:

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

Potency assay, off target (cells): In HEK-293 cells, WZ4003 did not inhibit phosphorylation of AMPK substrates.

Probe Selectivity in Cell:

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

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

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).

(last updated: 6 May 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

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).

(last updated: 15 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP 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.

(last updated: 17 Jun 2016 )