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BioAssay: AID 612077

Ratio of Ki for resting human sodium channel Nav1.7 expressed in human HEK293 cells to Ki for inactivated human sodium channel Nav1.7 expressed in human HEK293 cells

Clinical human genetic studies have recently identified the tetrodotoxin (TTX) sensitive neuronal voltage gated sodium channel Nav1.7 (SCN9A) as a critical mediator of pain sensitization. Herein, we report structure-activity relationships for a novel series of 2,4-diaminotriazines that inhibit hNav1.7. Optimization efforts culminated in compound 52, which demonstrated pharmacokinetic properties more ..
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Unspecified(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 612077
Data Source: ChEMBL (762088)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-05-26

Data Table ( Complete ):           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..
Tested Compounds:
Description:
Title: Identification of a potent, state-dependent inhibitor of Nav1.7 with oral efficacy in the formalin model of persistent pain.

Abstract: Clinical human genetic studies have recently identified the tetrodotoxin (TTX) sensitive neuronal voltage gated sodium channel Nav1.7 (SCN9A) as a critical mediator of pain sensitization. Herein, we report structure-activity relationships for a novel series of 2,4-diaminotriazines that inhibit hNav1.7. Optimization efforts culminated in compound 52, which demonstrated pharmacokinetic properties appropriate for in vivo testing in rats. The binding site of compound 52 on Nav1.7 was determined to be distinct from that of local anesthetics. Compound 52 inhibited tetrodotoxin-sensitive sodium channels recorded from rat sensory neurons and exhibited modest selectivity against the hERG potassium channel and against cloned and native tetrodotoxin-resistant sodium channels. Upon oral administration to rats, compound 52 produced dose- and exposure-dependent efficacy in the formalin model of pain.
(PMID: 21634377)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Assay Cell Type: HEK293

Target Type: Target is a single protein chain

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

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