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BioAssay: AID 373705

Agonist activity at turkey P2Y1 receptor expressed in human 1321N1 cells assessed as increase in intracellular calcium concentration by dual-excitation spectrofluorimetric analysis

P2Y nucleotide receptors (P2YRs) are attractive pharmaceutical targets. Most P2YR agonists proposed as drugs consist of a nucleotide scaffold, but their use is limited due to their chemical and enzymatic instabilities. To identify drug candidates, we developed non-hydrolyzable P2YR agonists. We synthesized ATP-beta,gamma-CH(2) analogues 2-4, and evaluated their chemical and metabolic stabilities more ..
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 Tested Compounds
 Tested Compounds
All(5)
 
 
Active(4)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(5)
 
 
Active(4)
 
 
Inactive(1)
 
 
AID: 373705
Data Source: ChEMBL (521734)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-08-23

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=P2Y purinoceptor 1; Short=P2Y1; AltName: Full=6H1 orphan receptor; AltName: Full=ATP receptor; AltName: Full=Purinergic receptor
Description ..   
Comment ..   

Gene:P2RY1     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 4
Description:
Title: Identification of hydrolytically stable and selective P2Y(1) receptor agonists.

Abstract: P2Y nucleotide receptors (P2YRs) are attractive pharmaceutical targets. Most P2YR agonists proposed as drugs consist of a nucleotide scaffold, but their use is limited due to their chemical and enzymatic instabilities. To identify drug candidates, we developed non-hydrolyzable P2YR agonists. We synthesized ATP-beta,gamma-CH(2) analogues 2-4, and evaluated their chemical and metabolic stabilities and activities at P2Y(1,2,4,6) receptors. Analogues 2-4 exhibited t(1/2) values of 14.5-65 h in gastric juice pH. They were completely resistant to alkaline phosphatase for 30 min at 37 degrees C and slowly hydrolyzed in human blood serum (t(1/2) 12.7-71.9 h). In comparison to ATP, analogues 2-4 were barely hydrolyzed by nucleoside triphosphate diphosphohydrolases, NTPDase1,2,3,8 (< 8% hydrolysis), and nucleotide pyrophosphatases, NPP1,3 (< or = 10% hydrolysis). Analogues 2 and 4B were selective agonists of the P2Y(1)R with EC(50)s of 0.08 and 17.2 microM, respectively. These features make analogues 2 and 4B potential therapeutic agents for health disorders involving the P2Y(1)R.
(PMID: 18760862)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Functional
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Test Type: In vitro
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
2Activity activity commentActivity activity commentString
3Activity standard flagActivity standard flagInteger
4Activity qualifierActivity qualifierString
5Activity published valueActivity published valueFloat
6Activity standard valueActivity standard valueFloat
7Activity binding domainsActivity binding domainsString
8EC50 activity commentEC50 activity commentString
9EC50 standard flagEC50 standard flagInteger
10EC50 qualifierEC50 qualifierString
11EC50 published valueEC50 published valueFloatnM
12EC50 standard valueEC50 standard valueFloatnM
13EC50 binding domainsEC50 binding domainsString
14EC50 activity commentEC50 activity commentString
15EC50 standard flagEC50 standard flagInteger
16EC50 qualifierEC50 qualifierString
17EC50 published valueEC50 published valueFloatμM
18EC50 standard valueEC50 standard valueFloatnM
19EC50 binding domainsEC50 binding domainsString

* Activity Concentration.

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