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BioAssay: AID 705436

Inhibition of human recombinant GAA assessed as hydrolysis of bovine liver glycogen by Amplex red oxidase assay

Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Many disease-causing mutated GAA retain enzymatic activity but are not translocated from endoplasmic reticulum (ER) to lysosomes. Enzyme replacement therapy (ERT) is the only treatment for Pompe disease but remains expensive, inconvenient, and does more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 705436
Data Source: ChEMBL (873179)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-05-25

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Lysosomal alpha-glucosidase; AltName: Full=Acid maltase; AltName: Full=Aglucosidase alfa; Contains: RecName: Full=76 kDa lysosomal alpha-glucosidase; Contains: RecName: Full=70 kDa lysosomal alpha-glucosidase; Flags: Precursor
Description ..   
Protein Family: GH31_MGAM_SI_GAA
Comment ..   

Gene:GAA     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Discovery of a novel noniminosugar acid alpha glucosidase chaperone series.

Abstract: Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Many disease-causing mutated GAA retain enzymatic activity but are not translocated from endoplasmic reticulum (ER) to lysosomes. Enzyme replacement therapy (ERT) is the only treatment for Pompe disease but remains expensive, inconvenient, and does not reverse all disease manifestations. It was postulated that small molecules which aid in protein folding and translocation to lysosomes could provide an alternate to ERT. Previously, several iminosugars have been proposed as small-molecule chaperones for specific LSDs. Here we identified a novel series of noniminosugar chaperones for GAA. These moderate GAA inhibitors are shown to bind and thermostabilize GAA and increase GAA translocation to lysosomes in both wild-type and Pompe fibroblasts. AMDE and physical properties studies indicate that this series is a promising lead for further pharmacokinetic evaluation and testing in Pompe disease models.
(PMID: 22834902)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

Protein Target Class: enzyme hydrolase

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1INH activity commentINH activity commentString
2INH standard flagINH standard flagInteger
3INH qualifierINH qualifierString
4INH published valueINH published valueFloatnM
5INH standard valueINH standard valueFloatnM

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