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VX-745

ATP-competitive inhibitor of MAPK14

Structure

Information

  • MAPK14
  • ATP-competitive inhibitor
  • 50-100 nM

In Vitro Validations

Uniprot ID: Q16539
Target Class: Protein kinase
Target SubClass: CMGC
Potency: KD
Potency Value: 2.8 nM
Potency Assay: KD was determined in a kinase binding assay. The IC50 (0.009 uM) was determined using a spectrophotometric coupled-enzyme assay.
PDB ID for probe-target interaction (3D structure): 3FC1
Target aliases:
Mitogen-activated protein kinase 14, SAPK2A, MXI2, ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : KD MAPK11 74 nM
Potency assay (off target): VX-745 was 20-fold selective for MAPK14 (p38alpha) > MAPK11 (p38beta) in IC50 assays. VX-745 was tested for kinase binding activity in a panel of 317 kinases showing <10 uM activity against 11 kinases (ABL1, BLK,CSF1R, DDR1, FGR, FYN, LCK, LYN, PDGFRB, SRC, YES).
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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This is a selective probe with some off-target activity against p38β; it is able to cross the blood-brain barrier.

(last updated: 23 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This probe has a pretty good selectivity towards p38alpha with effects on peripheral blood mononuclear cells (PBMCs) and on a rheumatoid arthritis mouse model.

(last updated: 1 Jul 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Effective inhibition of p38α should be achievable at concentrations between 50-100 nM. The reported Ki for p38β is 220 nM as determined in α spectrophotometric coupled-enzyme assay using recombinant protein. The Kd for other kinases such as DDR1 is reported to be above 1000 nM. This compound is a fairly selective p38 MAPKα inhibitor with a 20-fold window to p38 MAPKβ based on assessment in an activity assay. It is also useful as an in vivo probe.

(last updated: 3 Jul 2017 )