PXD060171

PXD060171 is an original dataset announced via ProteomeXchange.

Title	Discovery of a Small Molecule Secreted Clustering Enhancer that Improves Memory in Alzheimer's Disease Mice
Description	Here, we present findings from a drug discovery program aimed at developing small molecules that enhance brain sCLU levels and assessed their impact on AD pathology and cognition. A high-throughput screening campaign identified two classes of epigenetic modulators to increase sCLU levels, and medicinal chemistry efforts led to the development BET inhibitor new chemical entities with enhanced potency, drug-like properties, and oral brain bioavailability. Lead candidate, DDL-357, increased brain sCLU as well as proteins crucial for mitochondrial function, synaptic plasticity, and disease relevant protein aggregate clearance in AD mouse models. DDL-357 reduced p-tau and improved memory, presenting a promising multifaceted therapeutic approach for Alzheimer's treatment.
HostingRepository	PRIDE
AnnounceDate	2026-03-30
AnnouncementXML	Submission_2026-03-29_16:20:35.999.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD060171
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 HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-24 13:59:56	ID requested
⏵ 1	2026-03-29 16:20:36	announced

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]

10.6019/PXD060171;

submitter keyword: Alzheimers Disease, epigenetic modulator, memory improvement,secreted Clustering enhancer

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

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/PXD060171

PRIDE project URI

• PRIDE
  1. PXD060171
     1. Label: PRIDE project
     2. Name: Discovery of a Small Molecule Secreted Clustering Enhancer that Improves Memory in Alzheimer's Disease Mice