AX15836

Reagent Authentication Certificate:

Chemical Probes Portal AX15836.pdf

Protein target name:

MAPK7

Mechanism of action:

ATP-competitive inhibitor

Recommended Concentration for use in cells:

500 nM

Probe Availability

Tocris (1883429-22-8)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:6880

Entrez gene ID:

5598

UNIPROT ID:

Q13164

Target alias:

ERK5, mitogen-activated protein kinase 7, BMK1, ERK4, PRKM7

Probe Details

Chemical Probes Portal ID:

CPP792

PubChem CID:

122705989

SMILES string:

O=C1N(C)C2=CN=C(NC3=CC=C(C(N4CCC(N5CCN(C)CC5)CC4)=O)C=C3OCC)N=C2N(S(=O)(C)=O)C6=CC=CC=C16

InChi Key:

HTFNVAVTYILUCF-UHFFFAOYSA-N

Orthogonal probe:

BAY-885XMD8-92

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

8 nM

Potency assay:

KiNativ (www.kinativ.com)

Off target activity

Potency (off target):

Off target protein and potency:

BRD4 >1 uMkinases other than ERK5 > 1 uM

Potency assay (off target):

other kinases: KiNativ (www.kinativ.com)

Probe Selectivity in Vitro:

BRD4: DiscoveRx (https://www.discoverx.com/targets/epigenetics/bromodomain)

In cell validation

On target activity in cells

Potency in cells:

9 nM

Potency assay (cells):

KiNativ - in cell assay The compound was tested in PBMCs, endothelial cells, and oncogenic cell lines. In HeLa cells, AX15836 inhibited EGF-dependent ERK5 autophosphorylation.

Target engagement assay (cells):

Indirect, KiNativ assay

Off target activity in cells

Potency in cells, off target:

IC50

Off target protein and potency (cells):

kinases other than ERK5 > 1 uM

Potency assay, off target (cells):

KiNativ

Probe Selectivity in Cell:

AX15836 was not active in an E-selectin HUVEC assay, whereas other dual inhibitors of ERK5 and BET Bromodomains were (e.g., XMD8-92).

In vivo validation

Organism:

mouse, CD-1

Dose:

50 mg/kg

Route of delivery:

Oral

Plasma half life:

2.7 hr

Cmax:

1.5 uM

Tmax:

1.7 hr

Primary Reference

Reference (doi):

10.1073/pnas.1609019113

Reference (PMID):

27679845

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

This probe might be suitable for in vivo studies via non-standard dosing technologies (minipump or IP injection, twice daily with CYP inhibitor co-dosing) but not enough ADME data are provided to know which technology could work.

Dec 12 2016 - 12:45pm

A thorough exploration of the cellular effects of the compound is presented, but the DMPK data are not sufficiently good to allow in vivo evaluation via standard oral or IV dosing.

Mar 23 2017 - 11:35am

The probe is a potent and selective ERK5 inhibitor. The data look convincing, and selectivity against other kinases is particularly strong (limited other selectivity data disclosed aside from key bromodomain targets). Importantly, data are presented for target engagement within the cell and cellular and isolated biochemical potencies are similar. Recommended for use in vitro and/or in cells. No data were ncluded to support use of this probe in model organisms.

Mar 30 2017 - 6:57pm

AX15836

Probe Availability

Probe Information

Target Details

ERK5, mitogen-activated protein kinase 7, BMK1, ERK4, PRKM7

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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AX15836

Probe Availability

Probe Information

Target Details

ERK5, mitogen-activated protein kinase 7, BMK1, ERK4, PRKM7

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?