PXD034351-2

PXD034351 is an original dataset announced via ProteomeXchange.

Title	System-wide profiling of drug residence time by proteome integral solubility alteration assay
Description	Most drugs used in the clinic and drug candidates target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present a new Residence Time Proteome Integral Solubility Alteration (ResT-PISA) assay which provides monitoring temporal protein solubility profiles after drug removal in either cell lysate or intact cells, quantifying the lifetime of the drug-target interaction. A compressed version of the assay measures the integral under the off-curve and enables the multiplexing of binding affinity proxy measurements with residence time assessment into a single proteomic analysis. We introduce a combined scoring system for three parametric dimensions to improve prioritization of targets. By providing complementary information to other characteristics of drug-target interaction, ResT-PISA approach can become a useful tool in drug development and precision medicine.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:02.123.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Beusch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-06 02:18:21	ID requested
1	2023-01-06 08:14:04	announced
⏵ 2	2023-11-14 08:57:02	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: target engagement, drug development, thermal proteome profiling.,Efficacy target, lead compound optimization, target prioritization, binding affinity, precision medicine, target occupancy

Roman Zubarev
contact affiliation	Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden
contact email	roman.zubarev@ki.se
lab head
Christian Beusch
contact affiliation	Division of Chemistry I Department of Medical Biochemistry & Biophysics Karolinska Institutet
contact email	christian.beusch@ki.se
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/2023/01/PXD034351

PRIDE project URI

• PRIDE
  1. PXD034351
     1. Label: PRIDE project
     2. Name: System-wide profiling of drug residence time by proteome integral solubility alteration assay