ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 77 citations in OpenAlex.
- GM1 gangliosidosis type II: Results of a 10-year prospective study.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Observational
- Review
- Ganglioside GM1 and the Central Nervous System.International journal of molecular sciences · 2023Review
- Article
- spJournal of enzyme inhibition and medicinal chemistry · 2022Article
- Article
- Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis.Molecules (Basel, Switzerland) · 2022Article
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- GM1 Gangliosidosis: Mechanisms and Management.The application of clinical genetics · 2021Review
- GM1 Gangliosidosis-A Mini-Review.Frontiers in genetics · 2021Review
- Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes andMolecules (Basel, Switzerland) · 2020Article
- Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses.International journal of molecular sciences · 2019Review
- Lysosomes as a therapeutic target.Nature reviews. Drug discovery · 2019Review
- Thiol-ene "Click" Synthesis and Pharmacological Evaluation ofMolecules (Basel, Switzerland) · 2019Article
- Probing the Inhibitor versus Chaperone Properties of sp²-Iminosugars towards Human β-Glucocerebrosidase: A Picomolar Chaperone for Gaucher Disease.Molecules (Basel, Switzerland) · 2018Article
- Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.Frontiers in pharmacology · 2017Review
- Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Review
- Structural basis of pharmacological chaperoning for human β-galactosidase.The Journal of biological chemistry · 2014Article
- Emerging novel concept of chaperone therapies for protein misfolding diseases.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2014Review
- New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.PloS one · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosomal β-galactosidase (β-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use of small molecule ligands of β-Gal as pharmacological chaperones (PCs) for the treatment of GM1 gangliosidosis brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated the effect of bicyclic 1-deoxygalactonojirimycin (DGJ) derivative of the sp(2)-iminosugar type, namely 5N,6S-(N'-butyliminomethylidene)-6-thio-1- deoxygalactonojirimycin (6S-NBI-DGJ), as a novel PC for human mutant β-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human β-Gal in a competitive manner and was able to protect this enzyme from heat-induced degradation. Computational analysis supported that the rigid glycone bicyclic core of 6S-NBI-DGJ binds to the active site of the enzyme, with the aglycone N'-butyl substituent, in a precise E-orientation, located at a hydrophobic region nearby. Chaperone potential profiling indicated significant increases of enzyme activity in 24 of 88 β-Gal mutants, including four common mutations. Finally, oral administration of 6S-NBI-DGJ ameliorated the brain pathology of GM1 gangliosidosis model mice. These results suggest that 6S-NBI-DGJ is a novel PC that may be effective on a broad range of β-Gal mutants.
Indexed as
Identifiers
What OpenQuestion holds
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.