FS-694

Inhibitor Type I½ of MAPK14

Structure

Information

  • MAPK14
  • Inhibitor Type I½
  • 100 nM

In Vitro Validations

Uniprot ID: Q16539
Target Class: Kinase
Target SubClass: CMGC
Potency: IC50
Potency Value: 0.2 nM
Potency Assay: Elisa
PDB ID for probe-target interaction (3D structure): 5TCO
Structure-activity relationship: yes
Target aliases:
Mitogen-activated protein kinase 14, SAPK2A, MXI2, ...

DOI Reference: 10.1021/jm301539x

Uniprot ID: Q16539
Target Class: Kinase
Target SubClass: CMGC
Potency: Kd
Potency Value: 1.5 nM
Potency Assay: Cell free DiscoverX
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Mitogen-activated protein kinase 14, SAPK2A, MXI2, ...

DOI Reference: 10.1021/jm301539x

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Off targets detected in DX screen inactive in cells

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SERP ratings and comments


SERP Ratings

In Cell Rating

SERP Comments:

FS-694 is a dual active “type 1.5” inhibitor for P38-alpha (MAPK14) and P38-beta (MAPK11).  Broad kinase selectivity at 1 µM shows that the compound is extremely selective.  Off target activities include casein kinase 1 epsilon (CSNK1E) which is essentially completely inhibited in the discoverX panel screen at 1 µM, but no activity is seen in follow up in cells at 20 µM.  Some inhibition of P38-gamma is observed – no IC50 is reported but this is likely to be considerably weaker than the alpha/beta inhibition.  Relatively slow binding kinetics are observed with a residence time of around 4 minutes.  It has been previously noted that Type I and Type II kinase inhibitors can lead to different downstream consequences; FS-694 is a Type 1.5 inhibitor.  It is recommended that other tool compounds are used in parallel to check whether different results are obtained, for example Type I: Skepinone-L (related structure to FS-694) and VX-745 (unrelated), Type Il SR-318, BIRB769.  A negative control compound is also available.

(last updated: 24 Sept 2020 )