{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["22(5)"],"submitter":["Campagna J"],"pubmed_abstract":["Inhibition of amyloid precursor protein (APP) beta-site cleaving enzyme 1 (BACE1) has been a target for Alzheimer's disease (AD) therapeutic development. Here, we report our identification of APP-selective BACE1 (ASBI) inhibitors that are selective for APP as the substrate and BACE1 as the target enzyme. A known fluoro aminohydantoin (FAH) inhibitor compound was identified by screening a compound library for inhibition of BACE1 cleavage of a maltose binding protein (MBP)-conjugated-APPC125 substrate followed by optimization and IC50 determination using the P5-P5' activity assay. Optimization of the screening hit led to candidate FAH65, which displays selectivity for inhibition of APP cleavage with little activity against other BACE1 substrates neuregulin 1 (NRG1) or p-selectin glycoprotein"],"journal":["Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics"],"pagination":["e00610"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12491701"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease."],"pmcid":["PMC12491701"],"pubmed_authors":["Poksay K","Campagna J","Descamps O","Bredesen D","Lee J","Cohn W","Peters-Libeu C","Zhang Q","Zhu C","Jagodzinska B","Spilman P","John V","Jun M","Elias C","Gorostiza O","Padder S","Wi D"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease.","description":"Inhibition of amyloid precursor protein (APP) beta-site cleaving enzyme 1 (BACE1) has been a target for Alzheimer's disease (AD) therapeutic development. Here, we report our identification of APP-selective BACE1 (ASBI) inhibitors that are selective for APP as the substrate and BACE1 as the target enzyme. A known fluoro aminohydantoin (FAH) inhibitor compound was identified by screening a compound library for inhibition of BACE1 cleavage of a maltose binding protein (MBP)-conjugated-APPC125 substrate followed by optimization and IC50 determination using the P5-P5' activity assay. Optimization of the screening hit led to candidate FAH65, which displays selectivity for inhibition of APP cleavage with little activity against other BACE1 substrates neuregulin 1 (NRG1) or p-selectin glycoprotein","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-04T02:00:46.571Z","creation":"2026-05-04T03:13:22.029Z"},"accession":"S-EPMC12491701","cross_references":{"pubmed":["40399225"],"doi":["10.1016/j.neurot.2025.e00610"]}}