BAY-3827

Protein target name:

PRKAA1, RPS6KA1

Mechanism of action:

Inhibitor, ATP competitor

Recommended Concentration for use in cells:

~~150 nM~~

Reviewer suggested Concentration for use in cells:

500-1000 nM

Probe Availability

DC Chemicals

SGC Donated Chemical Probes

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CAMK

HUGO ID:

HGNC:9376 HGNC:10430

Entrez gene ID:

5562 6195

UNIPROT ID:

Q13131 Q15418

Target alias:

AMPK, AMPKa1, HU-1, MAPKAPK1, MAPKAPK1A, RSK, RSK1, p90Rsk

Probe Details

Chemical Probes Portal ID:

CPP1997

Probe alias:

BAY3827

PubChem CID:

134817183

SMILES string:

CCc1ccccc1C(=O)Nc2n[nH]c3c(C)c(F)c(cc23)C4C(=C(C)N(C)C(=C4C#N)C)C#N

InChi Key:

OZFFKOSQNBBYCA-UHFFFAOYSA-N

Control compound:

BAY-974

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

1.4 and 15 nM (High/Low ATP)

Potency assay:

High potency in biochemical PRKAA1 assay with IC50 = 1.4 nM @ 10 µM ATP; 15 nM @ 2 mM ATP (Bayer in house); IC50 = 7 nM (Eurofins @ 1 µM) RPS6KA1(h): IC50 = 9.1 nM (Eurofins @ 1 µM)

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

3AQV

Off target activity

Probe Selectivity in Vitro:

Selectivity > 500 fold against 322 out of 329 off-kinases tested; Most potent off-kinases @ 1µM: RPS6KA3 (IC50 = 52 nM (Eurofins)), RPS6KA2 (IC50 = 24 nM (Eurofins)), RPS6KA6 (IC50 = 37 nM (Bayer in house)), FLT3 (IC50 = 119 nM (Bayer in house)), RPS6KA5 (IC50 = 43 nM (Eurofins)), MST3 (IC50 = 94 nM (Eurofins))

In cell validation

On target activity in cells

Potency in cells:

IC50

150 nM

Potency assay (cells):

Active in cellular mechanistic assay (150 nM) demonstrating cellular target engagement Additional proof for on target activity: ATP-competitive binding mode demonstrated.

Primary Reference

Reference (doi):

10.1007/s13402-020-00584-8

Reference (PMID):

33492659

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

2 review(s)

Rating for use in Model Organisms

no rating

SAB Members

SAB Comments

AMPK is an important kinase in energy metabolism and regulation, yet there is no reported quality tool compounds beside BAY-3827. The compound demonstrates cellular target engagement by inhibiting phosphorylation of ACC1 on Ser79. The compound is also quite selective when tested at 1 μM concentration against 331 kinases at 10 μM ATP. Nevertheless, it does carry off-target activities against RSK1/2/3/4 - when measured in Eurofins radioactive kinase assays at 10 μM ATP, the IC50 values for RSK1/2/3/4 and MSK1 (RPS6KA5) are within ~5-fold of reported values for AMPKα1 and AMPKα2. Without data comparing the potency of BAY-3827 against AMPK and RSK1/2/3/4 at physiological concentration of 1 mM ATP (or in cellular mechanistic assays), the exact fold selectivity is difficult to assess. Given the lack of parallel tool compounds also targeting AMPK from alternative chemical scaffolds, one may consider use of selective RSK1/2/3/4 inhibitors, for example LJH685 or LJI308, as control for any cellular effects due to RSK1/2/3/4 inhibition.

Mar 24 2021 - 10:11am

BAY-3827

Probe Availability

Probe Information

Target Details

AMPK, AMPKa1, HU-1, MAPKAPK1, MAPKAPK1A, RSK, RSK1, p90Rsk

Probe Details

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

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BAY-3827

Probe Availability

Probe Information

Target Details

AMPK, AMPKa1, HU-1, MAPKAPK1, MAPKAPK1A, RSK, RSK1, p90Rsk

Probe Details

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?