PXD060173 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Discovery of a Small Molecule Secreted Clustering Enhancer that Improves Moemory in Alzheimer's Disease Mice |
| Description | Here, we present findings from our drug discovery program to identify small molecules that enhance sCLU levels and assess their impact on AD pathology and cognition in a murine model of AD. A high-throughput screening campaign identified two classes of epigenetic modulators that increase sCLU levels with subsequent medicinal chemistry efforts leading to bromodomain and extraterminal (BET) inhibitor new chemical entities (NCEs) with enhanced potency, drug-like properties, and oral brain bioavailability. The lead candidate NCE, DDL-357, increased brain sCLU in the murine ApoE4-TR:5xFAD model of AD in a subchronic study. In a follow-up chronic study in the murine 3XTg AD model, DDL-357 reduced phosho-tau in brain and lead to improvements in mouse performance in the Barnes maze memory testing paradigm. Proteomic analysis of brain tissue from both AD models revealed changes in proteins involved in mitochondrial function and synaptic plasticity. These findings reveal the potential of sCLU enhancement as a target for therapeutic development in AD and support the continued assessment of the lead candidate. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-03-30 |
| AnnouncementXML | Submission_2026-03-29_16:33:19.046.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD060173 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Jesus Campagna |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-01-24 15:54:40 | ID requested | |
| ⏵ 1 | 2026-03-29 16:33:19 | announced | |
Publication List
| 10.6019/PXD060173; |
| 10.1038/s44386-025-00009-2; |
| Cohn W, Campagna J, Wi D, Lee JT, Beniwal S, Elezi G, Zhu C, Jagodzinska B, Whitelegge J, Damoiseaux R, John V, Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer's disease mice. NPJ Drug Discov, 2(1):7(2025) [pubmed] |
Keyword List
| submitter keyword: epigenetic modulator, Alzheimer's disease, memory improvement,secreted Clustering enhancer |
Contact List
| Varghese John |
|---|
| contact affiliation | The Drug Discovery Lab, Mary S. Easton Center for Alzheimer’s Disease Research, Department of Neurology, David Geffen School of Medicine, 710 Westwood Plaza, University of California Los Angeles, Los Angeles, CA 90095, USA |
| contact email | VJohn@mednet.ucla.edu |
| lab head | |
| Jesus Campagna |
|---|
| contact affiliation | UCLA |
| contact email | jcampagna@mednet.ucla.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD060173 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD060173
- Label: PRIDE project
- Name: Discovery of a Small Molecule Secreted Clustering Enhancer that Improves Moemory in Alzheimer's Disease Mice
