FS-694

Protein target name:

MAPK14

Mechanism of action:

Inhibitor Type I½

Recommended Concentration for use in cells:

100 nM

Probe Availability

freely available upon request from SGC

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:6876

Entrez gene ID:

1432

UNIPROT ID:

Q16539

Target alias:

CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2, PRKM14, PRKM15, RK, SAPK2A, p38, p38ALPHA

Probe Details

Chemical Probes Portal ID:

CPP1842

PubChem CID:

71545859

ChEMBL ID:

CHEMBL2316207

SMILES string:

C1Cc2cc(ccc2C(c2cc(ccc12)C(NCCN1CCOCC1)=O)=O)Nc1ccc(c(c1)NC(c1ccccc1)=O)F

InChi Key:

JWZSSEWMVYKYKW-UHFFFAOYSA-N

Control compound:

FM-743

Orthogonal probe:

Skepinone-LSR-318VX-745

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50, KD

0.2, 1.5 nM

Potency assay:

Elisa; Cell free, DiscoverX

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

5TCO

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

Off targets detected in DX screen inactive in cells

In cell validation

On target activity in cells

Potency in cells:

IC50

14.9 nM Alpha16.9 nM Beta

Potency assay (cells):

NanoBRET

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

XTT (HEK cells)assay. Not toxic at highest assay concentration (30 µM)

Primary Reference

Reference (doi):

10.1021/jm301539x 10.1002/anie.201701185

Reference (PMID):

23270382 28397331

External Resources

Available data:

SGC additional analysis

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

Part of the Donated Chemical Probes initiative from SGC.

SAB Rating

Rating for use in Cells

1 review(s)

Rating for use in Model Organisms

no rating

SAB Members

SAB 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.

Sep 24 2020 - 11:20am

FS-694

Probe Availability

Probe Information

Target Details

CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2, PRKM14, PRKM15, RK, SAPK2A, p38, p38ALPHA

Probe Details

In vitro validation

In cell validation

Toxicity

Primary Reference

External Resources

Supporting Organizations

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FS-694

Probe Availability

Probe Information

Target Details

CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2, PRKM14, PRKM15, RK, SAPK2A, p38, p38ALPHA

Probe Details

In vitro validation

In cell validation

Toxicity

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?