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BioAssay: AID 643560

Inhibition of P38alpha in human whole blood assessed as inhibition of LPS-induced MK2 phosphorylation incubated for 30 mins prior to LPS challenge measured after 45 mins by flow cytometry

Structure-activity relationship (SAR) investigations of a novel class of triazolopyridazinone p38alpha mitogen activated protein kinase (MAPK) inhibitors are disclosed. From these studies, increased in vitro potency was observed for 2,6-disubstituted phenyl moieties and N-ethyl triazolopyridazinone cores due to key contacts with Leu108, Ala157 and Val38. Further investigation led to the more ..
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 Tested Compounds
 Tested Compounds
All(9)
 
 
Active(9)
 
 
 Tested Substances
 Tested Substances
All(9)
 
 
Active(9)
 
 
 Related BioAssays
 Related BioAssays
AID: 643560
Data Source: ChEMBL (801008)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2013-11-17

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Mitogen-activated protein kinase 14; Short=MAP kinase 14; Short=MAPK 14; AltName: Full=Cytokine suppressive anti-inflammatory drug-binding protein; Short=CSAID-binding protein; Short=CSBP; AltName: Full=MAP kinase MXI2; AltName: Full=MAX-interacting protein 2; AltName: Full=Mitogen-activated protein kinase p38 alpha; Short=MAP kinase p38 alpha; AltName: Full=Stress-activated protein kinase 2a; Short=SAPK2a
Description ..   
Protein Family: Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase
Comment ..   

Gene:MAPK14          More BioActivity Data..
BioActive Compounds: 9
Description:
Title: Identification of triazolopyridazinones as potent p38alpha inhibitors.

Abstract: Structure-activity relationship (SAR) investigations of a novel class of triazolopyridazinone p38alpha mitogen activated protein kinase (MAPK) inhibitors are disclosed. From these studies, increased in vitro potency was observed for 2,6-disubstituted phenyl moieties and N-ethyl triazolopyridazinone cores due to key contacts with Leu108, Ala157 and Val38. Further investigation led to the identification of three compounds, 3g, 3j and 3m that are highly potent inhibitors of LPS-induced MAPKAP kinase 2 (MK2) phosphorylation in 50% human whole blood (hWB), and possess desirable in vivo pharmacokinetic and kinase selectivity profiles.
(PMID: 22196117)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 10188

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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