PXD034351 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034351
- Label: PRIDE project
- Name: System-wide profiling of drug residence time by proteome integral solubility alteration assay