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Target not currently curated in GtoImmuPdb

Target id: 3101

Nomenclature: O-GlcNAcase

Family: Hydrolases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 916 10q24.32 OGA O-GlcNAcase
Mouse - 916 19 38.75 cM Oga O-GlcNAcase
Rat - 916 1q54 Oga O-GlcNAcase
Previous and Unofficial Names Click here for help
MEA5 | MGEA5 | NCOAT | glycoside hydrolase O-GlcNAcase | O-GlcNAc hydrolase
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction Click here for help
EC Number:

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Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MK-8719 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.1 pKi 3
pKi 8.1 (Ki 7.9x10-9 M) [3]
Description: In vitro enzyme inhibition assay.
thiamet-G Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.7 pKi 4
pKi 7.7 (Ki 2.1x10-8 M) [4]
MK-8719 Small molecule or natural product Ligand has a PDB structure Rn Inhibition 7.3 pEC50 3
pEC50 7.3 (EC50 5.27x10-8 M) [3]
Description: Determined in an ELISA-based assay with rat PC12 cells to measure EC50 values for elevation of all protein O-GlcNAc levels in the presence of test compound.
LY3372689 Small molecule or natural product Hs Inhibition 8.6 pIC50 1
pIC50 8.6 (IC50 2.36x10-9 M) [1]
Description: Inhibition of OGA enzyme activity in vitro
View species-specific inhibitor tables
Inhibitor Comments
Asceneuron have developed ASN120290 (previously ASN-561; structure not yet disclosed) as a brain-permeable and orally active small-molecule O-GlcNAcase enzyme inhibitor. It is reported in a 2018 review of in-development tau-based therapeutics that ASN120290 is being progressed to Phase 2 clinical trial, but there are no records for this agent (or ASN-561) on, or any citable data in PubMed articles (as far as we can ascertain). Asceneuron's patent WO2017144639A1 claims glycosidase inhibitors for the treatment of tauopathies [2].
General Comments
Post-translational O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins is a widely used mechanism that is crucial for regulating various cellular processes. The modifications are dynamic, with O-linked GlcNAc transferase (OGT) adding the O-GlcNAc modifications to protein serine and threonine residues, and O-GlcNAcase (OGA) removing them. The absence of O-GlcNAc chains leaves the serines and threonines available for phosphorylation. Two variants of the protein are produced from the human OGA gene. Both retain O-GlcNAcase enzymatic function.
Multiple lines of evidence indicate that aberrant phosphorylation of the tau protein drives its aggregation and the accumulation of toxic neurofibrillary tangles. Pharmacological blockade of O-GlcNAcase (i.e. to prevent O-GlcNAc removal and decrease phosphorylation) is being investigated as a novel mechanism to reduce tau hyperphosphorylation. Selective small-molecule O-GlcNAcase inhibitors are therefore being scrutinised for clinical utility in the treatment/prevention of neurodegenerative tauopathies, including Alzheimer's disease. To date, clinical progress has focussed on disease modification in patients with progressive supranuclear palsy, which is a rapidly progressing neurodegenerative disorder for which no current effective therapy exists..


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1. Dreyfus NJF, Lindsay-Scott PJ. (2018) N-[4-fluoro-5-[[(2s,4s)-2-methyl-4-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]-1-piperidyl]methyl]thiazol-2-yl]acetamide as oga inhibitor. Patent number: WO2018140299A1. Assignee: Eli Lilly And Company. Priority date: 27/01/2017. Publication date: 02/08/2018.

2. Quattropani A, Kulkarni SS, Giri AG. (2017) Glycosidase inhibitors. Patent number: WO2017144639A1. Assignee: Asceneuron SA. Priority date: 25/02/2016. Publication date: 31/08/2017.

3. Selnick HG, Hess JF, Tang C, Liu K, Schachter JB, Ballard JE, Marcus J, Klein DJ, Wang X, Pearson M et al.. (2019) Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. J Med Chem, 62 (22): 10062-10097. [PMID:31487175]

4. Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ et al.. (2008) A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol, 4 (8): 483-90. [PMID:18587388]

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