XMD8-92

ATP-competitive inhibitor of MAPK7

Structure

Information

Protein target names: MAPK7

Mechanism of action: ATP-competitive inhibitor

In Vitro Validations

Uniprot ID: Q13164
Target Class: Protein kinase
Target SubClass: CMGC
Potency: KD
Potency Value: 80 nM
Potency Assay: ATP-binding displacement assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Mitogen-activated protein kinase 7, PRKM7, ERK5, B ...

DOI Reference: 10.1016/j.ccr.2010.08.008

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating

Comments:

This compound inhibits the BET family of bromodomain-containing proteins and shouldn't be used as an ERK5 inhibitor.  Substantially all of the reported biological activity for this compound derives from BET inhibition, not from ERK5 inhibition.

This compound should not be used as an ERK5 inhibitor in cellular or in vivo experiments.

(last updated: 16 May 2016 )

SERP Ratings

In Cell Rating

Comments:

This compound is very selective as measured by broad profiling at DiscoverX and in a KiNativ experiment, and it blocks ERK5 in cells at about 1 micromolar. Improving the cellular activity would be a good next step.

(last updated: 20 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

XMD8-92 is a potent and selective inhibitor of BMK1 with a KD of 80 nM. Its selectivity was determined by evaluation against a panel of 402 kinases. It has a KD of 190, 890, and 600 nM against DCAMKL2, TNK1, and PLK4, respectively. It inhibits growth factor-induced activation of BMK1 at 1 uM in HeLa cells. PK studies showed it to be orally bioavailable and having a half life of 2 hours by IV dosing. XMD8-92 was shown to be active in xenograft models with 50 mg/kg, twice daily IP dosing.

(last updated: 28 Apr 2017 )

Portal Comments

The probe was re-scored by the SERP member, taking into consideration, the BET off-target effects.

(last updated: 1 Aug 2022)