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BioAssay: AID 456221

Inhibition of amino acid transport system xc- in human SNB19 cells assessed as [3H]L-glutamate uptake 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(5)
 
 
Unspecified(5)
 
 
 Tested Substances
 Tested Substances
All(5)
 
 
Unspecified(5)
 
 
 Related BioAssays
 Related BioAssays
AID: 456221
Data Source: ChEMBL (607279)
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
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM
7IC50 data validityIC50 data validityString
8IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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