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BioAssay: AID 325617

Agonist activity at human aryl hydrocarbon receptor

Protein kinases play a pivotal role in cell signaling, and dysregulation of many kinases has been linked to disease development. A large number of kinase inhibitors are therefore currently under investigation in clinical trials, and so far seven inhibitors have been approved as anti-cancer drugs. In addition, kinase inhibitors are widely used as specific probes to study cell signaling, but more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 325617
Data Source: ChEMBL (473643)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-25
Modify Date: 2014-08-23

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Aryl hydrocarbon receptor; Short=Ah receptor; Short=AhR; AltName: Full=Class E basic helix-loop-helix protein 76; Short=bHLHe76; Flags: Precursor
Description ..   
Protein Family: PAS
Comment ..   

Gene:AHR     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.

Abstract: Protein kinases play a pivotal role in cell signaling, and dysregulation of many kinases has been linked to disease development. A large number of kinase inhibitors are therefore currently under investigation in clinical trials, and so far seven inhibitors have been approved as anti-cancer drugs. In addition, kinase inhibitors are widely used as specific probes to study cell signaling, but systematic studies describing selectivity of these reagents across a panel of diverse kinases are largely lacking. Here we evaluated the specificity of 156 validated kinase inhibitors, including inhibitors used in clinical trials, against 60 human Ser/Thr kinases using a thermal stability shift assay. Our analysis revealed many unexpected cross-reactivities for inhibitors thought to be specific for certain targets. We also found that certain combinations of active-site residues in the ATP-binding site correlated with the detected ligand promiscuity and that some kinases are highly sensitive to inhibition using diverse chemotypes, suggesting them as preferred intervention points. Our results uncovered also inhibitor cross-reactivities that may lead to alternate clinical applications. For example, LY333'531, a PKCbeta inhibitor currently in phase III clinical trials, efficiently inhibited PIM1 kinase in our screen, a suggested target for treatment of leukemia. We determined the binding mode of this inhibitor by x-ray crystallography and in addition showed that LY333'531 induced cell death and significantly suppressed growth of leukemic cells from acute myeloid leukemia patients.
(PMID: 18077363)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
2EC50 activity commentEC50 activity commentString
3EC50 standard flagEC50 standard flagInteger
4EC50 qualifierEC50 qualifierString
5EC50 published valueEC50 published valueFloatnM
6EC50 standard valueEC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
Classification
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