ArticleNature protocols2015
Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry.
Article in Nature protocols, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 329 papers.
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Who cites it
329 citing papers in PubMed.
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- Cell painting and thermal proteome profiling for inference of drug targets and mechanism of action.Molecular systems biology · 2026Article
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- 4-Chloro-7-Nitrobenzofurazan induces ROS-mediated p53 dependent apoptosis in human fibrosarcoma cells.Molecular biology reports · 2026Article
- Integrated data-independent acquisition and thermal proteome profiling for proteomic characterization of lamotrigine-treated MCF-7 cells.Analytical and bioanalytical chemistry · 2026Article
- DORSSAA: Drug-Target interactOmics Resource Based on Stability/Solubility Alteration Assay.Molecular & cellular proteomics : MCP · 2026Article
- How Polyphenol Metabolites Spatiotemporally Reprogram Transcription Factors and Human Proteostasis: A Metabolite-Centric Framework.Current issues in molecular biology · 2026Review
- An approach for the systematic profiling of drug-induced remodeling of RNA-RBP (RNA-binding protein) interactions.RSC advances · 2026Article
- Biophysical Sensing Tools in Drug Discovery: Integrating Kinetics, Thermodynamics, Cellular Target Engagement and Structure.Sensors (Basel, Switzerland) · 2026Review
- SHP-1 agonist SC-43 limits methicillin-resistant Staphylococcus aureus infection through inhibition of heme biosynthesis.EMBO molecular medicine · 2026Article
- Global Proteomics Investigation of SAMT-247 Targets: An Antiviral Thioester that Acetylates Zinc Finger Proteins.bioRxiv : the preprint server for biology · 2026Article
- DeepDrugDiscovery identifies blood-brain barrier permeable autophagy enhancers for Alzheimer's disease.Nature biomedical engineering · 2026Article
- CK2 inhibition suppresses glial inflammation in models of neuroinflammation and neurodegeneration.Nature communications · 2026Article
- Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- Label-Free Target Discovery Strategy for Natural Active Products.Biomolecules · 2026Review
- Solubility based mechanistic profiling of combinatorial drug therapy.Nature communications · 2026Article
269 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The direct detection of drug-protein interactions in living cells is a major challenge in drug discovery research. Recently, we introduced an approach termed thermal proteome profiling (TPP), which enables the monitoring of changes in protein thermal stability across the proteome using quantitative mass spectrometry. We determined the intracellular thermal profiles for up to 7,000 proteins, and by comparing profiles derived from cultured mammalian cells in the presence or absence of a drug we showed that it was possible to identify direct and indirect targets of drugs in living cells in an unbiased manner. Here we demonstrate the complete workflow using the histone deacetylase inhibitor panobinostat. The key to this approach is the use of isobaric tandem mass tag 10-plex (TMT10) reagents to label digested protein samples corresponding to each temperature point in the melting curve so that the samples can be analyzed by multiplexed quantitative mass spectrometry. Important steps in the bioinformatic analysis include data normalization, melting curve fitting and statistical significance determination of compound concentration-dependent changes in protein stability. All analysis tools are made freely available as R and Python packages. The workflow can be completed in 2 weeks.
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