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BioAssay: AID 456224

Activity at amino acid transport system xc- in human SNB19 cells assessed as induction of L-glutamate efflux at 500 uM by fluorometric assay

Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System xc-. Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System xc-, the more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Inactive(7)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Inactive(7)
 
 
 Related BioAssays
 Related BioAssays
AID: 456224
Data Source: ChEMBL (607282)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-30
Modify Date: 2014-08-25

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Cystine/glutamate transporter; AltName: Full=Amino acid transport system xc-; AltName: Full=Calcium channel blocker resistance protein CCBR1; AltName: Full=Solute carrier family 7 member 11; AltName: Full=xCT
Description ..   
Protein Family: Transmembrane amino acid transporter protein
Comment ..   

Gene:SLC7A11     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Isoxazole analogues bind the system xc- transporter: structure-activity relationship and pharmacophore model.

Abstract: Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System xc-. Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System xc-, the latter is virtually devoid of activity. The most potent analogues were amino acid naphthyl-ACPA 7g, and hydrazone carboxylic acid, 11e Y=Y'=3,5-(CF(3))(2), which both inhibited glutamate uptake by the System xc- transporter with comparable potency to the endogenous substrate cystine, whereas in contrast the closed isoxazolo[3,4-d] pyridazinones 13 have significantly lower activity. A preliminary pharmacophore model has been constructed to provide insight into the analogue structure-activity relationships.
(PMID: 19932968)
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
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

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