ASN90 is a potent, selective, substrate-competitive O-GlcNAcase (OGA) inhibitor with IC50 of 10.2 nM.
ASN90 does not inhibit hexosaminidase (Hex).
ASN90 induced protein O-GlcNAcylation in plated human and rodent PBMC with similar potencies (EC50 of 209 and 489 nM for human and rodent PBMC, respectively).
ASN90 is chemically distinct from carbohydrate-type substrate mimetic OGA inhibitors such as Thiamet G and MK-8719. ASN90 binds to the OGA enzyme in the living rat brain and robustly elevates the O-GlcNAcylation of brain proteins, including both tau and α-synuclein, in vivo.
ASN90 exhibited therapeutic efficacy in preclinical models of both tau and α-synuclein pathology.
