SR-318

Type II Inhibitor of MAPK14, MAPK11

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe SR-318 is in the process of SERP review.

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Information

MAPK14
MAPK11

Type II Inhibitor

< 100 nM

Additional Data

SGC image SGC Chemical Probe Collection

Probe Availability:

In Vitro Validations

Uniprot ID: Q16539

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 5 nM

Potency Assay: Radiometric activity assay ProQinase

PDB ID for probe-target interaction (3D structure): 6SFO

Structure-activity relationship: yes

Target aliases:

Mitogen-activated protein kinase 14, SAPK2A, MXI2, ...

DOI Reference: 10.1021/acs.jmedchem.9b01227

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

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

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP 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.

(last updated: 2 Jun 2020 )