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PXD034351

PXD034351 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSystem-wide profiling of drug residence time by proteome integral solubility alteration assay
DescriptionMost 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:57:02.123.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristian Beusch
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-06-06 02:18:21ID requested
12023-01-06 08:14:04announced
22023-11-14 08:57:02announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: target engagement, drug development, thermal proteome profiling.,Efficacy target, lead compound optimization, target prioritization, binding affinity, precision medicine, target occupancy
Contact List
Roman Zubarev
contact affiliationChemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden
contact emailroman.zubarev@ki.se
lab head
Christian Beusch
contact affiliationDivision of Chemistry I Department of Medical Biochemistry & Biophysics Karolinska Institutet
contact emailchristian.beusch@ki.se
dataset submitter
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Dataset FTP location
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