ArticleThe FEBS journal2019
In vivo inactivation of glycosidases by conduritol B epoxide and cyclophellitol as revealed by activity-based protein profiling.
Article in The FEBS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review.International journal of molecular sciences · 2020Pooled it
- Long-term inhibition of lysosomal glucocerebrosidase activity promotes GPX4 stability and inhibits ferroptosis in dopaminergic neurons.Cell death & disease · 2026Article
- mTOR Inhibition Drives Mutation-Specific Remodeling of Lysosomal and Autophagic Pathways and GCase Activity in PBMC-Derived Macrophages from Patients with GBA1-Associated Parkinson's Disease.Current issues in molecular biology · 2026Article
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- Constraint-based modelling of metabolic dysregulation in Gaucher disease: mitochondrial dysfunction and disrupted cholesterol homeostasis.Orphanet journal of rare diseases · 2026Article
- Investigation of Carbonic Anhydrase Inhibition, Antioxidant Properties, and Selective Anticancer Activity of Methyl-Substituted Halogenated and Methoxy Conduritols.BioMed research international · 2026Article
- A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways.Biomolecules · 2025Review
- c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors.Antioxidants (Basel, Switzerland) · 2025Article
- Cultured Macrophage Models for the Investigation of Lysosomal Glucocerebrosidase and Gaucher Disease.International journal of molecular sciences · 2025Article
- Cytotoxic lymphocyte effector function is unaffected in patients with Gaucher disease.Frontiers in immunology · 2025Article
- Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2.NPJ Parkinson's disease · 2024Article
- Axonal Transport of Lysosomes Is Unaffected in Glucocerebrosidase-Inhibited iPSC-Derived Forebrain Neurons.eNeuro · 2023Article
- Biofabrication of anBiofabrication · 2023Article
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- Article
- Review
- HEPES-buffering of bicarbonate-containing culture medium perturbs lysosomal glucocerebrosidase activity.Journal of cellular biochemistry · 2022Article
- Synthesis of broad-specificity activity-based probes forOrganic & biomolecular chemistry · 2022Article
- Design, Synthesis and Structural Analysis of Glucocerebrosidase Imaging Agents.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Xylose-Configured Cyclophellitols as Selective Inhibitors for Glucocerebrosidase.Chembiochem : a European journal of chemical biology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocerebrosidase (GBA) is a lysosomal β-glucosidase-degrading glucosylceramide. Its deficiency causes Gaucher disease (GD), a common lysosomal storage disorder. Carrying a genetic abnormality in GBA constitutes at present the largest genetic risk factor for Parkinson's disease (PD). Conduritol B epoxide (CBE), a mechanism-based irreversible inhibitor of GBA, is used to generate cell and animal models for investigations on GD and PD. However, CBE may have additional glycosidase targets besides GBA. Here, we present the first in vivo target engagement study for CBE, employing a suite of activity-based probes to visualize catalytic pocket occupancy of candidate off-target glycosidases. Only at significantly higher CBE concentrations, nonlysosomal glucosylceramidase (GBA2) and lysosomal α-glucosidase were identified as major off-targets in cells and zebrafish larvae. A tight, but acceptable window for selective inhibition of GBA in the brain of mice was observed. On the other hand, cyclophellitol, a closer glucose mimic, was found to inactivate with equal affinity GBA and GBA2 and therefore is not suitable to generate genuine GD-like models. ENZYMES: Glucocerebrosidase (EC 3.2.1.45), nonlysosomal β-glucocerebrosidase (EC 3.2.1.45); cytosolic β-glucosidase (EC 3.2.1.21); α-glucosidases (EC 3.2.1.20); β-glucuronidase (EC 3.2.1.31).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.