Target Information
| Target General Information | Top | |||||
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| Target ID |
T21678
(Former ID: TTDC00016)
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| Target Name |
Alpha-galactosidase A (GLA)
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| Synonyms |
Melibiase; INN=Agalsidase; Alpha-D-galactoside galactohydrolase; Alpha-D-galactosidase A
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| Gene Name |
GLA
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Lysosomal disease [ICD-11: 5C56] | |||||
| Function |
A homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. Predominantly hydrolyzes ceramide trihexoside, and can catalyze the hydrolysis of melibiose into galactose and glucose.
Click to Show/Hide
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| BioChemical Class |
Glycosylase
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| UniProt ID | ||||||
| EC Number |
EC 3.2.1.22
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| Sequence |
MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEP
DSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQL ANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENL ADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIK SILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDL RHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIG GPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT MQMSLKDLL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T05RYU | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Migalastat | Drug Info | Approved | Fabry disease | [2] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | AVR-RD-01 | Drug Info | Phase 1/2 | Fabry disease | [3] | |
| 2 | PRX-102 | Drug Info | Phase 1/2 | Fabry disease | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Migalastat | Drug Info | [1], [5] | |||
| 2 | PRX-102 | Drug Info | [7] | |||
| Inhibitor | [+] 7 Inhibitor drugs | + | ||||
| 1 | (+)-5-deoxyadeenophorine | Drug Info | [8] | |||
| 2 | 2,5-dideoxy-2,5-imino-D-altritol | Drug Info | [9] | |||
| 3 | Alpha-D-Mannose | Drug Info | [10] | |||
| 4 | Beta-1-C-butenyl-1-deoxygalactonojirimycin | Drug Info | [9] | |||
| 5 | Beta-1-C-Butyl-1-deoxygalactonojirimycin | Drug Info | [9] | |||
| 6 | CALYSTEGINE B2 | Drug Info | [11] | |||
| 7 | Fucose | Drug Info | [10] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Galactose metabolism | |||||
| 2 | Glycerolipid metabolism | |||||
| 3 | Sphingolipid metabolism | |||||
| 4 | Glycosphingolipid biosynthesis - globo series | |||||
| 5 | Lysosome | |||||
| Pathwhiz Pathway | [+] 2 Pathwhiz Pathways | + | ||||
| 1 | Sphingolipid Metabolism | |||||
| 2 | Galactose Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Glycosphingolipid metabolism | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Sphingolipid metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | AT-1001: a high-affinity alpha3beta4 nAChR ligand with novel nicotine-suppressive pharmacology. Br J Pharmacol. 2015 Apr;172(7):1834-45. | |||||
| REF 2 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
| REF 3 | ClinicalTrials.gov (NCT03454893) FAB- GT Open-Label, Study Of Efficacy and Safety Of AVR-RD-01 for Treatment -Naive Subjects With Classic Fabry Disease. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT01981720) Extension Study of PRX-102 for 24 Months. U.S. National Institutes of Health. | |||||
| REF 5 | The pharmacological chaperone 1-deoxygalactonojirimycin increases alpha-galactosidase A levels in Fabry patient cell lines. J Inherit Metab Dis. 2009 Jun;32(3):424-40. | |||||
| REF 6 | Clinical pipeline report, company report or official report of Avrobio. | |||||
| REF 7 | Characterization of a chemically modified plant cell culture expressed human alpha-Galactosidase-A enzyme for treatment of Fabry disease. Mol Genet Metab. 2015 Feb;114(2):259-67. | |||||
| REF 8 | Flexible synthesis and biological evaluation of novel 5-deoxyadenophorine analogues. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3262-7. | |||||
| REF 9 | 2,5-Dideoxy-2,5-imino-d-altritol as a new class of pharmacological chaperone for Fabry disease. Bioorg Med Chem. 2010 Jun 1;18(11):3790-4. | |||||
| REF 10 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 11 | Identification of the glycosidase inhibitors swainsonine and calystegine B2 in Weir vine (Ipomoea sp. Q6 [aff. calobra]) and correlation with toxicity. J Nat Prod. 1995 Jun;58(6):878-86. | |||||
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