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BioAssay: AID 599097

Inhibition of human NaV1.7 expressed in HEK293 cells by [14C]guanidinium influx assay

Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of Na(V)1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold more ..
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 Tested Compounds
 Tested Compounds
All(57)
 
 
Active(44)
 
 
Unspecified(13)
 
 
 Tested Substances
 Tested Substances
All(57)
 
 
Active(44)
 
 
Unspecified(13)
 
 
AID: 599097
Data Source: ChEMBL (749248)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-02-15
Modify Date: 2014-08-23

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Sodium channel protein type 9 subunit alpha; AltName: Full=Neuroendocrine sodium channel; Short=hNE-Na; AltName: Full=Peripheral sodium channel 1; Short=PN1; AltName: Full=Sodium channel protein type IX subunit alpha; AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.7
Description ..   
Protein Family: Sodium ion transport-associated
Comment ..   

Gene:SCN9A     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 44
Description:
Title: Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain.

Abstract: Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of Na(V)1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold rigidification strategy then led to the discovery of XEN907, a novel spirooxindole Na(V)1.7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts.
(PMID: 21570288)
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: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: HEK293
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface 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 binding domainsIC50 binding domainsString

* Activity Concentration.

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