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BioAssay: AID 739829

Inhibition of mPGES1 (unknown origin) transfected in HEK293 cells co-expressing COX1 using arachidonic acid as substrate assessed as inhibition of PGE2 production incubated for 30 mins prior to arachidonic acid addition measured after 60 mins by HTRF assay

We have previously reported 7-bromo-2-(2-chrolophenyl)-imidazoquinolin-4(5H)-one (1) as a novel potent mPGES-1 inhibitor. To clarify the essential functional groups of 1 for inhibition of mPGES-1, we investigated this compound structure-activity relationship following substitution at the C(4)-position and N-alkylation at the N(1)-, the N(3)-, and the N(5)-positions of 1. To prepare the target more ..
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 Tested Compounds
 Tested Compounds
All(13)
 
 
Active(10)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(13)
 
 
Active(10)
 
 
Unspecified(3)
 
 
AID: 739829
Data Source: ChEMBL (952397)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-05-27

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Prostaglandin E synthase; AltName: Full=Microsomal glutathione S-transferase 1-like 1; Short=MGST1-L1; AltName: Full=Microsomal prostaglandin E synthase 1; Short=MPGES-1; AltName: Full=p53-induced gene 12 protein
Description ..   
Protein Family: MAPEG family
Comment ..   

Gene:PTGES     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 10
Description:
Title: Synthesis and biological evaluation of substituted imidazoquinoline derivatives as mPGES-1 inhibitors.

Abstract: We have previously reported 7-bromo-2-(2-chrolophenyl)-imidazoquinolin-4(5H)-one (1) as a novel potent mPGES-1 inhibitor. To clarify the essential functional groups of 1 for inhibition of mPGES-1, we investigated this compound structure-activity relationship following substitution at the C(4)-position and N-alkylation at the N(1)-, the N(3)-, and the N(5)-positions of 1. To prepare the target compounds, we established a good methodology for selective N-alkylation of the imidazoquinolin-4-one, that is, selective alkylation of 1 at the N(3)- and N(5)-positions was achieved by use of an appropriate base and introduction of a protecting group at the nitrogen atom in the imidazole part, respectively. Replacement of the C(4)-oxo group with nitrogen- or sulfur- linked substituents gave decreased inhibitory activity for mPGES-1, and introduction of alkyl groups on the nitrogen atom at the N(1)-, the N(3)-, and the N(5)-positions resulted in even larger loss of inhibitory activity. These results revealed that the C(4)-oxo group, and the hydrogen atoms at the N(5)-position and the imidazole part were the best substituents.
(PMID: 23394863)
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: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Assay Cell Type: HEK293

Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface 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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