AID	Name	Type	Comment
1467	qHTS Assay for Inhibitors of Human alpha-Galactosidase at pH 4.5.	confirmatory
2109	Confirmation of Inhibitors and Activators of Purified Human alpha-Galactosidase	confirmatory
2115	Confirmation of Inhibitors and Activators of Purified Human alpha-Glucosidase	confirmatory
2108	Confirmation of Inhibitors of Human alpha-Galactosidase Using Spleen Homogenate	confirmatory
2107	qHTS Assay for Inhibitors and Activators of Human alpha-Galactosidase From Spleen Homogenate	confirmatory

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

MLPCN Grant: 1R03MH084842-01
Assay Submitter (PI): Wei Zheng

NCGC Assay Overview:

Alpha-galactosidase is a homodimeric glycoprotein that hydrolyzes the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. Deficiency of this enzyme results in Fabry Disease with progressive accumulation of globotriaosylceramide and other glycosphingolipids in vascular endothelial cells that causes renal failure, myocardial infarction and stroke, and premature death in patients. It has been reported that the improper folding and trafficking of alpha-galactosidase resulting from the genetic mutations may account for a significant numbers of Fabry patients. 1-deoxygalactonojirimycin (DGJ), an inhibitor of alpha-galactosidase, was reported to exhibit the pharmacological chaperone activity which significant increased the mutant enzyme activity in cells. We optimized this alpha-galactosidase 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.

Please refer to other AIDs (1467) for detailed assay protocols.

This summary is written for the purposes of summarizing the probe activities from the project. No probes have yet been declared for this MLPCN project. The current results are from initial screening, and have not yet been validated. 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. The present results represent compounds with the largest PubChem score from AID 1467.

Grant Number: 1R03MH084842-01