PXD047093 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Development of inhibitors, probes, and PROTAC provides a complete toolbox to study PARK7 in the living cell |
Description | The innovation of combined chemical tools, such as small molecule inhibitors, activity-based probes (ABPs), and proteolysis targeting chimeras (PROTACs) for a specific target, not only advances clinical drug discovery but also provides a chemical toolbox to study the diverse biological perspective of targeted proteins. Here we report the development of such a chemical toolbox for the multifunctional human Parkinson disease protein 7 (PARK7/DJ-1) that has drawn attention as a candidate for drug discovery due to its involvement with Parkinson's disease and cancers. By combining structure-guided design, small library synthesis and high-throughput screening, we identified two compounds, JYQ-164 and JYQ-173, inhibiting PARK7 with high potency in vitro and in cell. These compounds covalently and selectively target its highly conserved and functionally essential residue, Cys106. Based on these compounds, we further developed two cell-permeable fluorescent probes, JYQ-192 and JYQ-196, with a SulfoCy5 dye to visualize PARK7 activity in living cells and a first-in-class PARK7 degrader JYQ-194 that selectively targets PARK7 to proteasomal degradation in human cells. Together, our study provides a valuable toolbox to advance the biology research of PARK7 in a cellular context and opens new opportunities for potential therapeutic application. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-16 |
AnnouncementXML | Submission_2024-06-15_23:11:01.962.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Rayman Tjokrodirijo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-11-20 03:36:13 | ID requested | |
⏵ 1 | 2024-06-15 23:11:02 | announced | |
Publication List
10.1021/acs.jmedchem.3c02410; |
Jia Y, Oyken M, Kim RQ, Tjokrodirijo RTN, de Ru AH, Janssen APA, Hacker SM, van Veelen PA, Geurink PP, Sapmaz A, Development of Inhibitors, Probes, and PROTAC Provides a Complete Toolbox to Study PARK7 in the Living Cell. J Med Chem, 67(10):7935-7953(2024) [pubmed] |
Keyword List
submitter keyword: PARK7, small molecule inhibitors, PROTACs, activity-based probes |
Contact List
Peter A. van Veelen |
contact affiliation | Head Proteomics Group, Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands |
contact email | P.A.van_Veelen@lumc.nl |
lab head | |
Rayman Tjokrodirijo |
contact affiliation | Leiden University Medical Center, Proteomics group |
contact email | R.T.N.Tjokrodirijo@lumc.nl |
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/2024/06/PXD047093 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047093
- Label: PRIDE project
- Name: Development of inhibitors, probes, and PROTAC provides a complete toolbox to study PARK7 in the living cell