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BioAssay: AID 446402

Agonist activity at human dopamine D3 receptor expressed in mouse AtT-20 cells assessed as stimulation of [35S]GTPgamma binding

Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Active(7)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Active(7)
 
 
 Related BioAssays
 Related BioAssays
AID: 446402
Data Source: ChEMBL (597580)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-08
Modify Date: 2014-05-25

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=D(3) dopamine receptor; AltName: Full=Dopamine D3 receptor
Description ..   
Protein Family: Serpentine type 7TM GPCR chemoreceptor Srsx
Comment ..   

Gene:DRD3     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 7
Description:
Title: Development of (S)-N6-(2-(4-(isoquinolin-1-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: potent in vivo activity in Parkinson's disease animal models.

Abstract: Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K(i)). Functional activity of selected compounds in stimulating GTPgammaS binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. SAR results identified compound (-)-24c (D-301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC(50) (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC(50)): 223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity. The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD.
(PMID: 20038106)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6EC50 activity commentEC50 activity commentString
7EC50 standard flagEC50 standard flagInteger
8EC50 qualifierEC50 qualifierString
9EC50 published valueEC50 published valueFloatnM
10EC50 standard valueEC50 standard valueFloatnM
11EC50 binding domainsEC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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