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BioAssay: AID 723507

Antagonist activity at recombinant EPAC2 (unknown origin) assessed 8-NBD-cAMP substrate fluorescence intensity by substrate competing assay

EPAC1 and EPAC2, two isoforms of exchange proteins directly activated by cAMP (EPAC), respond to the second messenger cAMP and regulate a wide variety of intracellular processes under physiological and pathophysiological circumstances. Herein, we report the chemical design, synthesis, and pharmacological characterization of three different scaffolds (diarylsulfones, N,N-diarylamines, and more ..
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 Tested Compounds
 Tested Compounds
All(34)
 
 
Active(24)
 
 
Unspecified(10)
 
 
 Tested Substances
 Tested Substances
All(34)
 
 
Active(24)
 
 
Unspecified(10)
 
 
 Related BioAssays
 Related BioAssays
AID: 723507
Data Source: ChEMBL (936073)
Depositor Category: Literature, Extracted
Deposit Date: 2013-11-07

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Rap guanine nucleotide exchange factor 4; AltName: Full=Exchange factor directly activated by cAMP 2; AltName: Full=Exchange protein directly activated by cAMP 2; Short=EPAC 2; AltName: Full=cAMP-regulated guanine nucleotide exchange factor II; Short=cAMP-GEFII
Description ..   
Protein Family: RasGEF
Comment ..   

Gene:RAPGEF4     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 24
Description:
Title: Identification and characterization of small molecules as potent and specific EPAC2 antagonists.

Abstract: EPAC1 and EPAC2, two isoforms of exchange proteins directly activated by cAMP (EPAC), respond to the second messenger cAMP and regulate a wide variety of intracellular processes under physiological and pathophysiological circumstances. Herein, we report the chemical design, synthesis, and pharmacological characterization of three different scaffolds (diarylsulfones, N,N-diarylamines, and arylsulfonamides) as highly potent and selective antagonists of EPAC2. Several selective EPAC2 antagonists have been identified including 20i (HJC0350), which has an apparent IC(50) of 0.3 muM for competing with 8-NBD-cAMP binding of EPAC2 and is about 133-fold more potent than cAMP. Compounds 1 (ESI-05), 14c (HJC0338), and 20i, selected from each series, have exhibited no inhibition of EPAC1-mediated Rap1-GDP exchange activity at 25 muM, indicating that they are EPAC2-specific antagonists. Moreover, live-cell imaging studies using EPAC1, EPAC2, or PKA FRET sensor also demonstrate that 20i functions as an EPAC2 specific antagonist.
(PMID: 23286832)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 104532

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface 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 valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 data validityIC50 data validityString

* Activity Concentration.

Data Table (Concise)
Classification
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