PXD045892-2

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

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PRIDE project URI

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