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BioAssay: AID 602238

qHTS for Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Metabolic Stability

Alpha-glucosidase is responsible for hydrolysis of terminal, non-reducing 1,4-linked alpha-D-glucose residues with release of alpha-D-glucose. It is a lysosomal hydrolase that is required for the degradation of a small percentage (1-3%) of cellular glycogen in human. Deficiency of this enzyme results in glycogen-storage disease type II (GSDII), also referred to as Pompe disease, an autosomal more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Active(2)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(2)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 602238
Data Source: NCGC (ALGU801)
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2012-01-30
Hold-until Date: 2013-01-29
Modify Date: 2013-01-29

Data Table ( Complete ):           Active    All
BioActive Compounds: 2
Depositor Specified Assays
AIDNameTypeComment
1473Quantitative High-Throughput Screen for Inhibitors and Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: SummarysummarySummary AID
Description:
Alpha-glucosidase is responsible for hydrolysis of terminal, non-reducing 1,4-linked alpha-D-glucose residues with release of alpha-D-glucose. It is a lysosomal hydrolase that is required for the degradation of a small percentage (1-3%) of cellular glycogen in human. Deficiency of this enzyme results in glycogen-storage disease type II (GSDII), also referred to as Pompe disease, an autosomal recessive disorder. Structurally normal glycogen is accumulated in lysosomes and cytoplasm in affected patients, primarily in muscle tissues. Excessive glycogen storage within lysosomes may interrupt normal functioning of other organelles and leads to cellular injury. In turn, this leads to enlargement and dysfunction of the entire organ involved (eg, cardiomyopathy and muscle weakness).

It has reported that the improper folding and trafficking of alpha-glucosidase resulting from the genetic mutations may account for a significant number of Pompe patients. N-butyl-deoxynojirimycin, an inhibitor of alpha-glucosidase, was reported to exhibit the pharmacological chaperone activity, which significantly increases the mutant enzyme activity in cells. We optimized this alpha-glucosidase assay in 1536-well plate format for identifying the novel small molecule inhibitors with the structures other than the sugar analogs in order to develop the new pharmacological chaperones.

The probe and other compounds were characterized in this metabolic stability assay to asses their properties.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Production Centers Network [MLPCN]

MLPCN Grant: MH084841
Assay Submitter (PI): Wei Zheng
Protocol
5uM of compound is incubated with mouse liver microsome; the reference compounds are verapamil and warfarin. Compounds are incubated and samples are analyzed with LC-MS/MS.
Comment
Compounds are "active" if percent remaining is equal or more than 90%; "inactive" if percent remaining is less than 90%.

PUBCHEM_ACTIVITY_SCORE is the closets whole number of percent remaining. If percent is > 100, score will be assigned as 100.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Microsomal StabilityInteger%
2Compound QC String
Additional Information
Grant Number: MH084841

Data Table (Concise)
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