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Gene and Protein Information ![]() |
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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 ![]() |
MEA5 | MGEA5 | NCOAT | glycoside hydrolase O-GlcNAcase | O-GlcNAc hydrolase |
Database Links ![]() |
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Alphafold | O60502 (Hs), Q9EQQ9 (Mm), Q8VIJ5 (Rn) |
BRENDA | 3.2.1.169 |
ChEMBL Target | CHEMBL5921 (Hs), CHEMBL4523449 (Mm), CHEMBL3351213 (Rn) |
Ensembl Gene | ENSG00000198408 (Hs), ENSMUSG00000025220 (Mm), ENSRNOG00000017822 (Rn) |
Entrez Gene | 10724 (Hs), 76055 (Mm), 154968 (Rn) |
Human Protein Atlas | ENSG00000198408 (Hs) |
KEGG Enzyme | 3.2.1.169 |
KEGG Gene | hsa:10724 (Hs), mmu:76055 (Mm), rno:154968 (Rn) |
OMIM | 604039 (Hs) |
Pharos | O60502 (Hs) |
RefSeq Nucleotide | NM_012215 (Hs), NM_023799 (Mm), NM_131904 (Rn) |
RefSeq Protein | NP_036347 (Hs), NP_076288 (Mm), NP_571979 (Rn) |
UniProtKB | O60502 (Hs), Q9EQQ9 (Mm), Q8VIJ5 (Rn) |
Wikipedia | OGA (Hs) |
Enzyme Reaction ![]() |
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 ClinicalTrials.gov, 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.. |
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]