PXD045712-1

PXD045712 is an original dataset announced via ProteomeXchange.

Title	Chemoproteomics-guided development of SLC15A4 inhibitors with anti-inflammatory activity
Description	SLC15A4 is an endolysosome-resident transporter intimately linked with autoinflammation and autoimmunity. Specifically, SLC15A4 is critical for Toll-like receptor (TLR) 7-9 as well as the nucleotide-binding oligomerization domain-containing protein (NOD) signaling in several immune cell subsets. Notably, SLC15A4 is essential for the development of systemic lupus erythematosus in murine models and is associated with autoimmune conditions in humans. Despite its therapeutic potential, to our knowledge no chemical probes have been developed that target SLC15A4. Here, we use an integrated chemical proteomics approach to develop a suite of chemical tools, including first-in-class functional inhibitors, for SLC15A4. We demonstrate SLC15A4 inhibitors described herein suppress endolysosomal TLR and NOD functions in a variety of human and mouse immune cells, furnish evidence of their ability to suppress inflammation in vivo and in clinical settings, and provide insights into their mechanism of action. Our findings establish SLC15A4 as a druggable target for the treatment of autoimmune/autoinflammatory conditions.
HostingRepository	PRIDE
AnnounceDate	2023-11-29
AnnouncementXML	Submission_2023-11-29_15:07:28.350.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tzu-Yuan Chiu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-26 14:02:22	ID requested
⏵ 1	2023-11-29 15:07:28	announced

Dataset with its publication pending

submitter keyword: anti-inflammatory, Chemoproteomics,SLC15A4

Christopher G. Parker
contact affiliation	Scripps Research
contact email	cparker@scripps.edu
lab head
Tzu-Yuan Chiu
contact affiliation	Scripps Research
contact email	tchiu@scripps.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/2023/11/PXD045712

PRIDE project URI

• PRIDE
  1. PXD045712
     1. Label: PRIDE project
     2. Name: Chemoproteomics-guided development of SLC15A4 inhibitors with anti-inflammatory activity