ArticleBioorganic & medicinal chemistry letters2017
Repurposing of Proton Pump Inhibitors as first identified small molecule inhibitors of endo-β-N-acetylglucosaminidase (ENGase) for the treatment of NGLY1 deficiency, a rare genetic disease.
Article in Bioorganic & medicinal chemistry letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 43 citations in OpenAlex.
- Downregulation of Endo-Beta-N-Acetylglucosaminidase in <italic>Caenorhabditis elegans</italic> Improves Stress Adaptivity.Cells, tissues, organs · 2026Article
- Cytosolic Peptide: N-Glycanase (NGLY1)-from Basic Biology to Genetic Disorder, NGLY1 Deficiency.Advances in experimental medicine and biology · 2026Review
- Article
- Systemic gene therapy corrects the neurological phenotype in a mouse model of NGLY1 deficiency.JCI insight · 2024Article
- Exome/Genome Sequencing in Undiagnosed Syndromes.Annual review of medicine · 2023Review
- Roles of Human Liver Cytochrome P450 Enzymes in Tenatoprazole Metabolism.Pharmaceutics · 2022Article
- Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach.Pharmaceutics · 2022Article
- Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.Nutrients · 2022Review
- NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.Cells · 2022Review
- Cytosolic O-GlcNAcylation and PNG1 maintain Drosophila gut homeostasis by regulating proliferation and apoptosis.PLoS genetics · 2022Article
- Why rare disease needs precision medicine-and precision medicine needs rare disease.Cell reports. Medicine · 2022Article
- Knowledge-based approaches to drug discovery for rare diseases.Drug discovery today · 2022Review
- Article
- NGLY1 Deficiency: A Rare Newly Described Condition with a Typical Presentation.Life (Basel, Switzerland) · 2021Article
- Recent Advances in the Chemical Biology ofMolecules (Basel, Switzerland) · 2021Review
- Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation.BMC medical genetics · 2020Article
- NGLY1 deficiency-A rare congenital disorder of deglycosylation.JIMD reports · 2020Article
- Selective Targeting of Virus Replication by Proton Pump Inhibitors.Scientific reports · 2020Article
- Identification of ebselen as a potent inhibitor of insulin degrading enzyme by a drug repurposing screening.European journal of medicinal chemistry · 2019Article
- Induced pluripotent stem cells for neural drug discovery.Drug discovery today · 2019Review
Corrections and comments
- Commented on byShort Takes.2019
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
N-Glycanase deficiency, or NGLY1 deficiency, is an extremely rare human genetic disease. N-Glycanase, encoded by the gene NGLY1, is an important enzyme involved in protein deglycosylation of misfolded proteins. Deglycosylation of misfolded proteins precedes the endoplasmic reticulum (ER)-associated degradation (ERAD) process. NGLY1 patients produce little or no N-glycanase (Ngly1), and the symptoms include global developmental delay, frequent seizures, complex hyperkinetic movement disorder, difficulty in swallowing/aspiration, liver dysfunction, and a lack of tears. Unfortunately, there has not been any therapeutic option available for this rare disease so far. Recently, a proposed molecular mechanism for NGLY1 deficiency suggested that endo-β-N-acetylglucosaminidase (ENGase) inhibitors may be promising therapeutics for NGLY1 patients. Herein, we performed structure-based virtual screening utilizing FDA-approved drug database on this ENGase target to enable repurposing of existing drugs. Several Proton Pump Inhibitors (PPIs), a series of substituted 1H-benzo [d] imidazole, and 1H-imidazo [4,5-b] pyridines, among other scaffolds, have been identified as potent ENGase inhibitors. An electrophoretic mobility shift assay was employed to assess the inhibition of ENGase activity by these PPIs. Our efforts led to the discovery of Rabeprazole Sodium as the most promising hit with an IC
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