Diaminocyclopentane-derived O-GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease

0560090 - MBÚ 2023 RIV GB eng J - Journal Article
Weber, P. - Mészáros, Zuzana - Jagecic, D. - Hribljan, V. - Mitrečic, D. - Bojarová, Pavla - Slámová, Kristýna - Vrba, J. - Kulik, Natalia - Křen, Vladimír - Stuetz, A. E.
Diaminocyclopentane-derived O-GlcNAcase inhibitors for combating tau hyperphosphorylation in Alzheimer's disease.
Chemical Communications. Roč. 58, č. 63 (2022), s. 8838-8841. ISSN 1359-7345. E-ISSN 1364-548X
R&D Projects: GA ČR(CZ) GF21-01948L
Institutional support: RVO:61388971
Keywords : primary human hepatocyteskinetic * kinetic-analysis * enzyme level * hepg2 cells * hexosaminidase * mechanisms * induction
OECD category: Biochemistry and molecular biology
Impact factor: 4.9, year: 2022
Method of publishing: Limited access
https://pubs.rsc.org/en/content/articlelanding/2022/CC/D2CC02712G

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.
Permanent Link: https://hdl.handle.net/11104/0333257