PXD053138

PXD053138 is an original dataset announced via ProteomeXchange.

Title	Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays - Revisions
Description	In response to an ever-increasing demand of new small molecules therapeutics, numerous chemical and genetic tools have been developed to interrogate compound mechanism of action. Owing to its ability to characterize compound-dependent changes in thermal stability, the proteome-wide thermal shift assay has emerged as a powerful tool in this arsenal. The most recent iterations have drastically improved the overall efficiency of these assays, providing an opportunity to screen compounds at a previously unprecedented rate. Taking advantage of this advance, we quantified 1.498 million thermal stability measurements in response to multiple classes of therapeutic and tool compounds (96 compounds in living cells and 70 compounds in lysates). When interrogating the dataset as a whole, approximately 80% of compounds (with quantifiable targets) caused a significant change in the thermal stability of an annotated target. There was also a wealth of evidence portending off-target engagement despite the extensive use of the compounds in the laboratory and/or clinic. Finally, the combined application of cell- and lysate-based assays, aided in the classification of primary (direct ligand binding) and secondary (indirect) changes in thermal stability. Overall, this study highlights the value of these assays in the drug development process by affording an unbiased and reliable assessment of compound mechanism of action.
HostingRepository	PRIDE
AnnounceDate	2025-02-13
AnnouncementXML	Submission_2025-02-13_06:59:18.582.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonathan Van Vranken
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-15 06:48:00	ID requested
⏵ 1	2025-02-13 06:59:19	announced

Van Vranken JG, Li J, Mintseris J, Wei TY, Sniezek CM, Gadzuk-Shea M, Gygi SP, Schweppe DK, Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays. Elife, 13():(2024) [pubmed]

10.7554/elife.95595;

submitter keyword: Thermal shift assay, Proteomics,Drug Discovery

Devin Schweppe
contact affiliation	Department of Genome Sciences, University of Washington, Seattle, WA 98195 USA
contact email	dkschwep@uw.edu
lab head
Jonathan Van Vranken
contact affiliation	Harvard Medical School
contact email	van@hms.harvard.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/2025/02/PXD053138

PRIDE project URI

• PRIDE
  1. PXD053138
     1. Label: PRIDE project
     2. Name: Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays - Revisions