AX15836

ATP-competitive inhibitor of MAPK7

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

MAPK7

ATP-competitive inhibitor

500 nM

DOI - 10.1073/pnas.1609019113

Probe Availability:

In Vitro Validations

Uniprot ID: Q13164

Target Class: Kinase

Target SubClass: CMGC

Potency: Kd

Potency Value: 8 nM

Potency Assay: KiNativ (www.kinativ.com)

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

Target aliases:

Mitogen-activated protein kinase 7, PRKM7, ERK5, B ...

DOI Reference: 10.1073/pnas.1609019113

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : Kd BRD4 >1 uM, kinases 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)

Potency in cells, off target : IC50 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).

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP 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.

(last updated: 11 Dec 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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.

(last updated: 22 Mar 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

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.

(last updated: 30 Mar 2017 )