Journal
CHEMICAL COMMUNICATIONS
Volume 58, Issue 63, Pages 8838-8841Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d2cc02712g
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Funding
- Czech-Austrian project - Czech Science Foundation [GA21-01948L]
- Czech-Austrian project - Austrian Science Fund [I5236]
- Orastem project of the Croatian Science Foundation [IP-16-6-9451]
- European Regional Development Fund as a Scientific Center of Excellence for Basic, Clinical, and Translational Neuroscience [KK.01.1.1.01.0007]
- Croatian Science Foundation
- Palacky University [RVO 61989592]
- Austrian Science Fund (FWF) [I5236] Funding Source: Austrian Science Fund (FWF)
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Potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-beta-d-glucosaminidase (OGA) have been developed for the treatment of Alzheimer's disease. Compound 13, for example, showed nanomolar OGA inhibition and 92,000-fold selectivity over human HexB. It was non-toxic and increased protein O-GlcNAcylation in murine neural cell culture, providing new alternatives for tauopathies treatment.
We developed potent and selective aminocyclopentane-derived inhibitors of human O-N-acetyl-beta-d-glucosaminidase (OGA) implicated in Alzheimer's disease. For example compound 13 was a nanomolar OGA inhibitor with 92 000-fold selectivity over human HexB. It was non-toxic and increased protein O-GlcNAcylation in the culture of murine neural cells, showing new alternatives in the treatment of tauopathies.
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