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BioAssay: AID 629369

Inhibition of human TAK1

The design, synthesis, and ability to inhibit p38alpha MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNFalpha production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 629369
Data Source: ChEMBL (786817)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-24

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Nuclear receptor subfamily 2 group C member 2; AltName: Full=Orphan nuclear receptor TAK1; AltName: Full=Orphan nuclear receptor TR4; AltName: Full=Testicular receptor 4
Description ..   
Protein Family: The ligand binding domain of the orphan nuclear receptors TR4 and TR2
Comment ..   

Gene:NR2C2     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: 1,7-Naphthyridine 1-oxides as novel potent and selective inhibitors of p38 mitogen activated protein kinase.

Abstract: The design, synthesis, and ability to inhibit p38alpha MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNFalpha production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked selectivity against other related kinases. After an extensive SAR exercise, several compounds from this series were identified as very potent p38alpha inhibitors. In vivo efficacy of some derivatives was demonstrated to reduce TNFalpha levels in an acute murine model of inflammation (ED(50) = 0.5 mg/kg in LPS-induced TNFalpha production when dosed orally 1.5 h prior to LPS administration). The oral efficacy was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally (ED(50) < 1 mg/kg).
(PMID: 21999461)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Classification
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