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 ..
Target
| Sequence: acid alpha-glucosidase preproprotein [Homo sapiens] Protein Family: GH31_MGAM_SI_GAA Gene:GAA Related Protein 3D Structures |
Depositor Specified Assays
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| AID | Name | Type | Comment |
|---|---|---|---|
| 1466 | qHTS Assay for Inhibitors of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease | confirmatory | |
| 2242 | qHTS Assay for Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease | confirmatory | |
| 2112 | qHTS Assay for Inhibitors and Activators of Human alpha-Glucosidase From Spleen Homogenate | confirmatory | |
| 2100 | qHTS Assay for Inhibitors and Activators of Human alpha-Glucosidase Cleavage of Glycogen | confirmatory | |
| 2113 | Confirmation of Inhibitors and Activators of Human alpha-Glucosidase From Spleen Homogenate | confirmatory | |
| 2115 | Confirmation of Inhibitors and Activators of Purified Human alpha-Glucosidase | confirmatory | |
| 2111 | Confirmation of Inhibitors and Activators of Human alpha-Glucosidase From Spleen Homogenate Using an Alternate Red Fluorescent Susbtrate | confirmatory | |
| 2110 | Confirmation of Inhibitors and Activators of Purified Human alpha-Glucosidase Using an Alternate Red Fluorescent Susbtrate | confirmatory | |
| 2108 | Confirmation of Inhibitors of Human alpha-Galactosidase Using Spleen Homogenate | confirmatory | |
| 2109 | Confirmation of Inhibitors and Activators of Purified Human alpha-Galactosidase | confirmatory | |
| 2107 | qHTS Assay for Inhibitors and Activators of Human alpha-Galactosidase From Spleen Homogenate | confirmatory | |
| 2101 | qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease | confirmatory | |
| 504681 | Inhibitors of Human alpha-Glucosidase: PBS Stability Profiling | other | |
| 540361 | Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Alpha-Galactosidase Counter Screen | confirmatory | |
| 602122 | qHTS for Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Fibroblast Translocation | other | |
| 602238 | qHTS for Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Metabolic Stability | other | |
| 2641 | qHTS Assay for Inhibitors of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Stabilizers of Alpha-Glucosidase Under Thermal Denaturation Conditions | other | |
| 504688 | Inhibitors of Human alpha-Glucosidase: Caco-2 Efflux Ratio Profiling | other | |
| 1467 | qHTS Assay for Inhibitors of Human alpha-Galactosidase at pH 4.5. | confirmatory | |
| 540341 | Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Glucocerebrosidase Counter Screen | confirmatory | |
| 2293 | Direct Measure of the Activation of Acid alpha-Glucosidase Catalytic Rate | other | |
| 602237 | qHTS for Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Aqueous Solubility | other | |
| 504686 | Inhibitors of Human alpha-Glucosidase: Caco-2 Cell Permeability Profiling | other | |
| 602239 | qHTS for Activators of Human alpha-Glucosidase as a Potential Chaperone Treatment of Pompe Disease: Metabolic Stability in presence of NADPH | other |
Description:
NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Production centers Network [MLPCN]
MLPCN Grant: 1R03MH084841-01
Assay Submitter (PI): Wei Zheng
NCGC Assay Overview:
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 is an activator of alpha-Glucosidase in purified in vitro assays, as well as tissue homogenate assays. This compound may be useful as a chemical chaperone of alpha-Glucosidase, though this has not yet been demonstrated for this compound.
NIH Molecular Libraries Probe Production centers Network [MLPCN]
MLPCN Grant: 1R03MH084841-01
Assay Submitter (PI): Wei Zheng
NCGC Assay Overview:
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 is an activator of alpha-Glucosidase in purified in vitro assays, as well as tissue homogenate assays. This compound may be useful as a chemical chaperone of alpha-Glucosidase, though this has not yet been demonstrated for this compound.
Protocol
Please refer to other AIDs (1466, 2242, 2112, 2100, 2113, 2115, 2111, 2110, 2108, 2109, 2107, 2101) for detailed assay protocols.
Comment
This summary is written for the purposes of summarizing the probe activities from the project. MLSCN probes are given a score of 100. Molecules in the prior art are given a score of 80. Other, less active molecules in the same chemical series as the probe molecules are given a score of 50. Molecules pending validation are given a score of 10. Inactive analogues from these series are given a score of 0.
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| Score | The BioAssay activity ranking score |  | Integer | |||
| 1 | Activity Summary | Nature of interaction of the sample with the enzyme. | String | |||
| 2 | alpha-Glucosidase Potency (Purified; Red Substrate) | The concentration of sample yielding half-maximal sample efficacy. | | Float | μM | |
| 3 | alpha-Glucosidase Potency (Tissue homogenate; Red Substrate) | The concentration of sample yielding half-maximal sample efficacy. | | Float | μM | |
| 4 | beta-Glucosidase Activity | Nature of interaction of the sample with the enzyme. | String | |||
| 5 | alpha-Galactosidase Activity | Nature of interaction of the sample with the enzyme. | String | |||
| 6 | alpha-Glucosidase Activity (Purified; Glycogen) | Nature of interaction of the sample with the enzyme. | String |
Additional Information
Grant Number: 1R03MH084841-01
Data Table (Concise)
Classification
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