PXD045892

PXD045892 is an original dataset announced via ProteomeXchange.

Title	Discovery of molecular glue degraders via isogenic morphological profiling
Description	Molecular glue degraders (MGDs) are small molecules that degrade proteins-of-interest via the ubiquitin-proteasome system. Historically, MGDs were discovered serendipitously. Current approaches for MGD discovery include cell-viability based drug screens or data mining of public transcriptomics and drug response datasets. The explored target space is consequently re-stricted to the essential proteins. Here we develop a high-throughput workflow for MGD discovery that also reaches the non-essential proteome. This workflow begins with the rapid synthesis of a compound library by Sulfur(VI) Fluoride Exchange chemistry coupled to a morphological profiling assay in isogenic cell lines that vary in levels of the E3 ligase CRBN. By com-paring the morphological changes induced by compound treatment across the isogenic cell lines, we were able to identify FL2-14 as a CRBN-dependent MGD targeting the non-essential protein GSPT2. We envision that this workflow would con-tribute to the discovery and characterization of MGDs targeting a wider range of proteins.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:15:06.859.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrea Rukavina
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carboxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-04 01:57:35	ID requested
1	2023-11-20 07:34:40	announced
⏵ 2	2024-10-22 06:15:07	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: neo-substrate,Cereblon, targeted protein degradation, molecular glue degrader, E3 ubiquitin ligase

Georg E. Winter
contact affiliation	CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences; Vienna, Austria
contact email	gwinter@cemm.oeaw.ac.at
lab head
Andrea Rukavina
contact affiliation	The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	arukavina@cemm.oeaw.ac.at
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/PXD045892

PRIDE project URI

• PRIDE
  1. PXD045892
     1. Label: PRIDE project
     2. Name: Discovery of molecular glue degraders via isogenic morphological profiling