AZ191

Reagent Authentication Certificate:

Chemical Probes Portal AZ191.pdf

Protein target name:

DYRK1B

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

20 nM - 3 uM

Probe Availability

Tocris (1594092-37-1)

MedChem Express (1594092-37-1)

MilliporeSigma (1594092-37-1)

Cayman (1594092-37-1)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:3092

Entrez gene ID:

9149

UNIPROT ID:

Q9Y463

Target alias:

AOMS3, MIRK

Probe Details

Chemical Probes Portal ID:

CPP132

Probe alias:

AZ 191, AZ-191

PubChem CID:

72716071

ChEMBL ID:

CHEMBL3421968

SMILES string:

CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=CC(=N3)C4=CN(C5=C4C=CN=C5)C)OC

InChi Key:

ZYVXTMKTGDARKR-UHFFFAOYSA-N

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

17 nM

Potency assay:

in vitro radioactivity-based substrate phosphorylation assay

Off target activity

Potency (off target):

IC50

Off target protein and potency:

DYRK1A 88 nMDYRK2 1,890 nM

Potency assay (off target):

In vitro radioactivity-based substrate phosphorylation assay

Probe Selectivity in Vitro:

In Kinomescan (DiscoverX) assessing >400 kinases, there were only 8 non-mutated kinase hits at 1 uM (CIT, DRAK1, DYRK1A, MEK5, MKNK2, PRKD2, RPS6KA4, YSK4).

In cell validation

On target activity in cells

Potency assay (cells):

In cells, AZ191 dose-dependently inhibited DYRK1B > DYRK1A substrate phosphorylation.

Target engagement assay (cells):

Indirect, inhibition of protein substrate phosphorylation

Primary Reference

Reference (doi):

10.1042/BJ20130461

Reference (PMID):

24134204

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

no rating

SAB Members

SAB Comments

Concentrations higher than a few micromolar are likely to inhibit other kinases.

Jun 11 2016 - 4:30am

AZ191 is claimed to have 5-10x selectivity over DYRK1A and >100x over DYRK2. This molecule has been tested against >400 kinases at 1 uM and only hits 9 of them. A range of cellular effects are reported as well as cellular markers of activity. This tool is recommended for use in preference to the older, less selective harmine and derivatives.

Jun 11 2016 - 4:30am

This compound is too promiscuous kinome-wide to be useful as a cellular inhibitor of DYRK1B.

Jun 30 2016 - 3:52am

AZ191

Probe Availability

Probe Information

Target Details

AOMS3, MIRK

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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AZ191

Probe Availability

Probe Information

Target Details

AOMS3, MIRK

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?