General Information of Drug Therapeutic Target (DTT) (ID: TT1B5PU)

DTT Name Glucosylceramidase (GBA)
Synonyms
SGTase; Lysosomal acid glucosylceramidase; Lysosomal acid GCase; Imiglucerase; GLUC; GC; D-glucosyl-N-acylsphingosine glucohydrolase; Cholesteryl-beta-glucosidase; Cholesterol glucosyltransferase; Beta-glucocerebrosidase; Beta-GC; Alglucerase; Acid beta-glucosidase
Gene Name GBA
DTT Type
Successful target
[1]
BioChemical Class
Glycosylase
UniProt ID
GLCM_HUMAN
TTD ID
T84173
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.2.1.45
Sequence
MEFSSPSREECPKPLSRVSIMAGSLTGLLLLQAVSWASGARPCIPKSFGYSSVVCVCNAT
YCDSFDPPTFPALGTFSRYESTRSGRRMELSMGPIQANHTGTGLLLTLQPEQKFQKVKGF
GGAMTDAAALNILALSPPAQNLLLKSYFSEEGIGYNIIRVPMASCDFSIRTYTYADTPDD
FQLHNFSLPEEDTKLKIPLIHRALQLAQRPVSLLASPWTSPTWLKTNGAVNGKGSLKGQP
GDIYHQTWARYFVKFLDAYAEHKLQFWAVTAENEPSAGLLSGYPFQCLGFTPEHQRDFIA
RDLGPTLANSTHHNVRLLMLDDQRLLLPHWAKVVLTDPEAAKYVHGIAVHWYLDFLAPAK
ATLGETHRLFPNTMLFASEACVGSKFWEQSVRLGSWDRGMQYSHSIITNLLYHVVGWTDW
NLALNPEGGPNWVRNFVDSPIIVDITKDTFYKQPMFYHLGHFSKFIPEGSQRVGLVASQK
NDLDAVALMHPDGSAVVVVLNRSSKDVPLTIKDPAVGFLETISPGYSIHTYLWRRQ
Function
Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramide/GlcCer into free ceramide and glucose. Thereby, plays a central role in the degradation of complex lipids and the turnover of cellular membranes. Through the production of ceramides, participates to the PKC-activated salvage pathway of ceramide formation. Also plays a role in cholesterol metabolism. May either catalyze the glucosylation of cholesterol, through a transglucosylation reaction that transfers glucose from glucosylceramide to cholesterol. The short chain saturated C8:0-GlcCer and the mono-unsaturated C18:0-GlcCer being the most effective glucose donors for that transglucosylation reaction. Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl-beta-D-glucoside to ceramide. Finally, may also hydrolyze cholesteryl-beta-D-glucoside to produce D-glucose and cholesterol.
KEGG Pathway
Other glycan degradation (hsa00511 )
Sphingolipid metabolism (hsa00600 )
Metabolic pathways (hsa01100 )
Lysosome (hsa04142 )
Reactome Pathway
Glycosphingolipid metabolism (R-HSA-1660662 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Taliglucerase alfa DM3PZXN Metabolic disorder 5C50-5D2Z Approved [1]
Velaglucerase alfa DM4BOAS Gaucher disease type I Approved [2]
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1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Isofagomine tartrate DM2RS0V Metabolic disorder 5C50-5D2Z Phase 2 [3]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Afegostat DMRWSKX Gaucher disease 5C56.0Y Discontinued in Phase 2 [4]
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2 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
N-Octyl-beta-valienamine DM39C47 Gaucher disease 5C56.0Y Preclinical [5]
NCGC607 DMXG0O1 Gaucher disease 5C56.0Y Preclinical [6]
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8 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(2R,3S,4S,5R)-2-hexylpiperidine-3,4,5-triol DMDS8AN Discovery agent N.A. Investigative [7]
(2R,3S,4S,5R)-2-nonylpiperidine-3,4,5-triol DMIQNX9 Discovery agent N.A. Investigative [7]
(2R,3S,4S,5R)-2-propylpiperidine-3,4,5-triol DM7GI94 Discovery agent N.A. Investigative [7]
1,5-Dideoxy-1,5-imino-D-xylitol DMZU1GD Discovery agent N.A. Investigative [8]
2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose DMOUG6Y Discovery agent N.A. Investigative [9]
L-Isofagomine DM6RKOC Discovery agent N.A. Investigative [8]
N-(Propylamide-acetophenone)-1-deoxynojirimycin DMXI4V8 Discovery agent N.A. Investigative [10]
N-(Propylamide-benzophenone)-1-deoxynojirimycin DMCZHBI Discovery agent N.A. Investigative [10]
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⏷ Show the Full List of 8 Investigative Drug(s)

References

1 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
2 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
3 Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry. Chembiochem. 2008 Nov 3;9(16):2650-62.
4 Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948.
5 Chemical modification of the beta-glucocerebrosidase inhibitor N-octyl-beta-valienamine: synthesis and biological evaluation of 4-epimeric and 4-O-(beta-D-galactopyranosyl) derivatives. Bioorg Med Chem. 2002 Jun;10(6):1967-72.
6 A New Glucocerebrosidase Chaperone Reduces alpha-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism. J Neurosci. 2016 Jul 13;36(28):7441-52.
7 Synthesis of new beta-1-C-alkylated imino-L-iditols: A comparative study of their activity as beta-glucocerebrosidase inhibitors. Bioorg Med Chem. 2010 Apr 1;18(7):2645-50.
8 In vitro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures. Bioorg Med Chem. 2008 Aug 1;16(15):7330-6.
9 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
10 Nanomolar affinity, iminosugar-based chemical probes for specific labeling of lysosomal glucocerebrosidase. Bioorg Med Chem. 2010 Jan 1;18(1):267-73.