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BioAssay: AID 663169

Competitive inhibition of Epac2 using fluorescent nucleotide analog 8-NBD-cAMP by fluorescence analysis relative to cAMP

Exchange proteins directly activated by cAMP (Epac) are a family of guanine nucleotide exchange factors that regulate a wide variety of intracellular processes in response to second messenger cAMP. To explore the structural determinants for Epac antagonist properties of high throughput screening (HTS) hit ESI-08, pyrimidine 1, a series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine analogues have been more ..
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 Tested Compounds
 Tested Compounds
All(19)
 
 
Unspecified(19)
 
 
 Tested Substances
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Unspecified(19)
 
 
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AID: 663169
Data Source: ChEMBL (820258)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-05-26

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Tested Compounds:
Description:
Title: 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP.

Abstract: Exchange proteins directly activated by cAMP (Epac) are a family of guanine nucleotide exchange factors that regulate a wide variety of intracellular processes in response to second messenger cAMP. To explore the structural determinants for Epac antagonist properties of high throughput screening (HTS) hit ESI-08, pyrimidine 1, a series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine analogues have been synthesized and evaluated for their activities for Epac inhibition. Structure-activity relationship (SAR) analysis led to the identification of three more potent Epac antagonists (6b, 6g, and 6h). These inhibitors may serve as valuable pharmacological probes for further elucidation of the physiological functions and mechanisms of Epac regulation. Our SAR results and molecular docking studies have also revealed that further optimization of the moieties at the C-6 position of pyrimidine scaffold may allow us to discover more potent Epac-specific antagonists.
(PMID: 22607683)
Comment
Putative Target:

ChEMBL Target ID: 104532
Target Type: SINGLE PROTEIN
Pref Name: Rap guanine nucleotide exchange factor 4
Synonyms: cAMP-GEFII;cAMP-regulated guanine nucleotide exchange factor II;EPAC 2;Exchange factor directly activated by cAMP 2;Exchange protein directly activated by cAMP 2;Rap guanine nucleotide exchange factor 4;
Gene Name: CGEF2 ;EPAC2;RAPGEF4;
Protein Accession: Q8WZA2;
Protein GI: 32171491;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: unclassified
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ratio IC50 activity commentRatio IC50 activity commentString
2Ratio IC50 standard flagRatio IC50 standard flagInteger
3Ratio IC50 qualifierRatio IC50 qualifierString
4Ratio IC50 published valueRatio IC50 published valueFloat
5Ratio IC50 standard valueRatio IC50 standard valueFloat

Data Table (Concise)
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