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BioAssay: AID 630387

Agonist activity at GPR35 in human U20S cells expressing beta-lactamase and GPR35-GA14-VP16 transcription factor fusion protein assessed as transcriptional activation after 5 hrs by tango beta-arrestin translocation reporter assay relative to zaprinast

Screening with dynamic mass redistribution (DMR) assays in a native cell line HT-29 led to identification of two novel series of chemical compounds, 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives, as GPR35 agonists. Of these, 2-(3-cyano-5-(3,4-dichlorophenyl)-4,5-dimethylfuran-2(5H)-ylidene)malononitrile (YE120) and more ..
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 Tested Compounds
 Tested Compounds
All(19)
 
 
Active(2)
 
 
Inactive(7)
 
 
Inconclusive(2)
 
 
Unspecified(8)
 
 
 Tested Substances
 Tested Substances
All(19)
 
 
Active(2)
 
 
Inactive(7)
 
 
Inconclusive(2)
 
 
Unspecified(8)
 
 
AID: 630387
Data Source: ChEMBL (787835)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-24

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=G-protein coupled receptor 35; AltName: Full=Kynurenic acid receptor; Short=KYNA receptor
Description ..   
Comment ..   

Gene:GPR35     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 2
Description:
Title: Discovery of 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives as G protein-coupled receptor 35 (GPR35) agonists.

Abstract: Screening with dynamic mass redistribution (DMR) assays in a native cell line HT-29 led to identification of two novel series of chemical compounds, 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives, as GPR35 agonists. Of these, 2-(3-cyano-5-(3,4-dichlorophenyl)-4,5-dimethylfuran-2(5H)-ylidene)malononitrile (YE120) and 6-bromo-3-methylthieno[3,2-b]thiophene-2-carboxylic acid (YE210) were found to be the two most potent GPR35 agonists with an EC(50) of 32.5 # 1.7 nM and 63.7 # 4.1 nM, respectively. Both agonists exhibited better potency than that of zaprinast, a known GPR35 agonist. DMR antagonist assays, knockdown of GPR35 with interference RNA, receptor internalization assays, and Tango beta-arrestin translocation assays confirmed that the agonist activity of these ligands is specific to GPR35. The present study provides novel chemical series as a starting point for further investigations of GPR35 biology and pharmacology.
(PMID: 21950657)
Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat%
5Activity standard valueActivity standard valueFloat%

Data Table (Concise)
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