BAY-3827

BAY-3827 : ATP competitive inhibitor of PRKAA1 and RPS6KA1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

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Information

PRKAA1
RPS6KA1

Inhibitor, ATP competitor

500-1000 nM

Additional Data

SGC image SGC Chemical Probe Collection

Probe Availability:

In Vitro Validations

Uniprot ID: Q13131

Target Class: Kinase

Target SubClass: CAMK

Potency: IC50

Potency Value: 1.4, 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)

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

Target aliases:

5'-AMP-activated protein kinase catalytic subunit ...

DOI Reference: 10.1007/s13402-020-00584-8

Uniprot ID: Q13131

Target Class: Kinase

Target SubClass: CAMK

Potency: IC50

Potency Value: 7 nM

Potency Assay: Eurofins @ 1 µM

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

Target aliases:

5'-AMP-activated protein kinase catalytic subunit ...

DOI Reference: 10.1007/s13402-020-00584-8

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

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)) Outside target family: Shows off-target activity in the GPCR scan: the closest hits are GABA/PBR (Ki = 222.4 nM) and DRD1 (Ki = 634.31 nM)

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 3 Aug 2020 )

SERP Ratings

In Cell Rating

SERP 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.

(last updated: 24 Mar 2021 )

SERP Ratings

In Cell Rating

(last updated: 22 Mar 2023 )