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BioAssay: AID 462811

Agonist activity at G-protein coupled P2Y1 receptor expressed in human 1321N1 cells assessed as increase in calcium by Fura2 assay

Dinucleoside polyphosphates exert their physiological effects via P2 receptors (P2Rs). They are attractive drug candidates, as they offer better stability and specificity compared to nucleotides, the most common P2 receptor ligands. The activation of pancreatic P2Y receptors by nucleotides increases insulin secretion. Therefore, in the current study, dinucleoside polyphosphate analogues more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Active(6)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Active(6)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 462811
Data Source: ChEMBL (613869)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-30
Modify Date: 2014-05-26

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 6
Description:
Title: A novel insulin secretagogue based on a dinucleoside polyphosphate scaffold.

Abstract: Dinucleoside polyphosphates exert their physiological effects via P2 receptors (P2Rs). They are attractive drug candidates, as they offer better stability and specificity compared to nucleotides, the most common P2 receptor ligands. The activation of pancreatic P2Y receptors by nucleotides increases insulin secretion. Therefore, in the current study, dinucleoside polyphosphate analogues (di-(2-MeS)-adenosine-5',5''-P(1),P(4),alpha,beta-methylene-tetraphosphate), 8, (di-(2-MeS)-adenosine-5',5''-P(1),P(4),beta,gamma-methylene-tetraphosphate), 9, and di-(2-MeS)-adenosine-5',5''-P(1),P(3),alpha,beta-methylene triphosphate, 10, were developed as potential insulin secretagogues. Analogues 8 and 9 were found to be agonists of the P2Y(1)R with EC(50) values of 0.42 and 0.46 microM, respectively, whereas analogue 10 had no activity. Analogues 8-10 were found to be completely resistant to hydrolysis by alkaline phosphatase over 3 h at 37 degrees C. Analogue 8 also was found to be 2.5-fold more stable in human blood serum than ATP, with a half-life of 12.1 h. Analogue 8 administration in rats caused a decrease in a blood glucose load from 155 mg/dL to ca. 100 mg/dL and increased blood insulin levels 4-fold as compared to basal levels. In addition, analogue 8 reduced a blood glucose load to normal values (80-110 mg/dL), unlike the commonly prescribed glibenclamide, which reduced glucose levels below normal values (60 mg/dL). These findings suggest that analogue 8 may prove to be an effective and safe treatment for type 2 diabetes.
(PMID: 20175517)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Putative Target:
ChEMBL Target ID: 10544
Target Type: SINGLE PROTEIN
Pref Name: Purinergic receptor P2Y1
Synonyms: ATP receptor;P2Y purinoceptor 1;P2Y1;Purinergic receptor;
Gene Name: P2RY1;
Protein Accession: P47900;
Protein GI: 1352692;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: membrane receptor 7tm1 smallmol nucleotide-like receptor purine receptor
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Functional
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
2EC50 activity commentEC50 activity commentString
3EC50 standard flagEC50 standard flagInteger
4EC50 qualifierEC50 qualifierString
5EC50 published valueEC50 published valueFloatnM
6EC50 standard valueEC50 standard valueFloatnM
7EC50 activity commentEC50 activity commentString
8EC50 standard flagEC50 standard flagInteger
9EC50 qualifierEC50 qualifierString
10EC50 published valueEC50 published valueFloatμM
11EC50 standard valueEC50 standard valueFloatnM

* Activity Concentration.

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