SR-318

Protein target name:

MAPK14

Mechanism of action:

Type II Inhibitor

Recommended Concentration for use in cells:

< 100 nM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:6878

Entrez gene ID:

5596

UNIPROT ID:

Q16539

Target alias:

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

Probe Details

Chemical Probes Portal ID:

CPP1874

Probe alias:

SR318

PubChem CID:

139030333

SMILES string:

C1CCC(CC1)CCCNC(c1ccc(CNC(c2cnn(c3ccccc3)c2N)=O)cc1)=O

InChi Key:

HXNUFFCHRIWTRZ-UHFFFAOYSA-N

Control compound:

SR-321

Orthogonal probe:

Skepinone-L, F-694VX-745

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

5 nM (Alpha) 32 nM (Beta)

Potency assay:

Radiometric activity assay ProQinase

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

6SFO

Structure-activity relationship:

yes

In cell validation

On target activity in cells

Potency in cells:

IC50

3.7 nM p38a 10 nM p38b

Potency assay (cells):

NanoBRET

Off target activity in cells

Potency assay, off target (cells):

NanoBRET

Probe Selectivity in Cell:

Closest off-targets found in KinomeScan: DDR1/2, KIT, ZAK, RSK4, MYLK4 show > 200-fold selective in NanoBRET assay

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.9b01227

Reference (PMID):

31702918

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

1 review(s)

SAB Members

SAB Comments

SR-318 displays exquisite selectivity for p38a/b vs other kinases. At 100nM, 90% p38a/b inhibition is observed in cells using NanoBRET while other kinases are basically uninhibited at this concentration. Interestingly, SR-318 has an inactive probe also listed in the original research article (compound 126) to use as a further experimental control. SR-318 displays good activity in a whole blood assay with a reasonable right shifting of potency due to plasma protein binding (IC50 = 240nM), demonstrating this probe’s utility in high serum assays. Given its activity in blood, this probe might potentially have utility in vivo. However, a pharmacokinetic study would be necessary to confirm this potential. No such study has been published as of May 2020.

Jun 2 2020 - 10:58am

SR-318

Probe Availability

Probe Information

Target Details

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

Probe Details

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

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SR-318

Probe Availability

Probe Information

Target Details

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

Probe Details

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?