Streamlined analysis of drug targets by proteome integral solubility alteration indicates organ-specific engagement

Tanveer Singh Batth (), Marie Locard-Paulet, Nadezhda T. Doncheva, Blanca Lopez Mendez, Lars Juhl Jensen and Jesper Velgaard Olsen ()
Additional contact information
Tanveer Singh Batth: University of Copenhagen
Marie Locard-Paulet: University of Copenhagen
Nadezhda T. Doncheva: University of Copenhagen
Blanca Lopez Mendez: University of Copenhagen
Lars Juhl Jensen: University of Copenhagen
Jesper Velgaard Olsen: University of Copenhagen

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Proteins are the primary targets of almost all small molecule drugs. However, even the most selectively designed drugs can potentially target several unknown proteins. Identification of potential drug targets can facilitate design of new drugs and repurposing of existing ones. Current state-of-the-art proteomics methodologies enable screening of thousands of proteins against a limited number of drug molecules. Here we report the development of a label-free quantitative proteomics approach that enables proteome-wide screening of small organic molecules in a scalable, reproducible, and rapid manner by streamlining the proteome integral solubility alteration (PISA) assay. We used rat organs ex-vivo to determine organ specific targets of medical drugs and enzyme inhibitors to identify drug targets for common drugs such as Ibuprofen. Finally, global drug profiling revealed overarching trends of how small molecules affect the proteome through either direct or indirect protein interactions.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53240-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53240-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53240-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().