XMD8-92

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

DOI - 10.1016/j.ccr.2010.08.008

Probe Availability:

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

Off-Target Selectivity Assesments

Potency end-point : KD DCAMKL2 190 nM, TNK1 890 nM, PLK4 600 nM

Potency assay (off target): XMD8-92 displaced ATP (>90%) at 10 uM against these related targets as well as DCAMKL1, but not for the remainder of the 402 kinases tested.

Potency in cells, off target : IC50 TNK1 10 uM, ACK1 18 uM

Potency assay, off target (cells): Assessed XMD8-92 in Kinativ assay in HeLa cells

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP 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

SERP 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

SERP Comments:

XMD8-92 is a potent and selective inhibitor of BMK1 with a K_D of 80 nM. Its selectivity was determined by evaluation against a panel of 402 kinases. It has a K_D 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)