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BioAssay: AID 456218

Inhibition of amino acid transport system xc- in human SNB19 cells assessed as [3H]L-glutamate uptake at 500 uM by liquid scintillation counting

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(18)
 
 
Unspecified(18)
 
 
 Tested Substances
 Tested Substances
All(18)
 
 
Unspecified(18)
 
 
 Related BioAssays
 Related BioAssays
AID: 456218
Data Source: ChEMBL (607276)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-30
Modify Date: 2013-11-16

Data Table ( Complete ):           All
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
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 103088

ChEMBL Target Type: Target is a single protein chain

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)
Classification
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