ArticleeLife2024
Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed.
- Cell painting and thermal proteome profiling for inference of drug targets and mechanism of action.Molecular systems biology · 2026Article
- Detergent selection as a determinant of protein melting behavior and drug-target interaction-calling in thermal stability proteomics.bioRxiv : the preprint server for biology · 2026Article
- Advances in proteomics research related to semaglutide: evidence from humans and animals.Journal of endocrinological investigation · 2026Review
- DORSSAA: Drug-Target interactOmics Resource Based on Stability/Solubility Alteration Assay.Molecular & cellular proteomics : MCP · 2026Article
- Comprehensive Chemoproteomics Unveils Selective HMG-CoA Synthase 1 Inhibitors for Targeting Mevalonate Metabolism in Cancer.Journal of the American Chemical Society · 2026Article
- Robotic perturbation proteomics and AI agents enable scalable drug mechanism discovery.bioRxiv : the preprint server for biology · 2026Article
- The proteomic landscape and temporal dynamics of human and mouse gastruloid development.Nature cell biology · 2026Article
- Selective TRPV2 Antagonists Derived from the Natural Product Piperlongumine Inhibit Cancer Cell Migration and Metastasis.ACS chemical biology · 2026Article
- Solubility based mechanistic profiling of combinatorial drug therapy.Nature communications · 2026Article
- Potent synthetic lethality between PLK1 and EYA family inhibitors in tumors of the central and peripheral nervous systems.Genes & development · 2026Article
- Bacterial ubiquitin ligase engineered for small molecule and protein target identification.The EMBO journal · 2026Article
- Defining the heterogeneous molecular landscape of lung cancer cell responses to epigenetic inhibition.Communications biology · 2026Article
- An expanded role for single-cell chemical genomics profiling in drug discovery.The Biochemical journal · 2026Review
- Solvent-induced partial cellular fixation decodes proteome-wide drug targets and downstream pathways in living cells.Nature communications · 2025Article
- Characterizing the quick-killing mechanism of action of azithromycin analogs against malaria parasites.Antimicrobial agents and chemotherapy · 2025Article
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.Journal of proteome research · 2025Article
- Recent Advances in Mass Spectrometry-Based Bottom-Up Proteomics.Analytical chemistry · 2025Review
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.bioRxiv : the preprint server for biology · 2024Article
- Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry.ACS infectious diseases · 2024Article
- High-throughput identification of calcium-regulated proteins across diverse proteomes.Cell reports · 2024Article
Corrections and comments
- Update of
Authors and funding
8 authors.
Funding
Abstract
In response to an ever-increasing demand of new small molecules therapeutics, numerous chemical and genetic tools have been developed to interrogate compound mechanism of action. Owing to its ability to approximate compound-dependent changes in thermal stability, the proteome-wide thermal shift assay has emerged as a powerful tool in this arsenal. The most recent iterations have drastically improved the overall efficiency of these assays, providing an opportunity to screen compounds at a previously unprecedented rate. Taking advantage of this advance, we quantified more than one million thermal stability measurements in response to multiple classes of therapeutic and tool compounds (96 compounds in living cells and 70 compounds in lysates). When interrogating the dataset as a whole, approximately 80% of compounds (with quantifiable targets) caused a significant change in the thermal stability of an annotated target. There was also a wealth of evidence portending off-target engagement despite the extensive use of the compounds in the laboratory and/or clinic. Finally, the combined application of cell- and lysate-based assays, aided in the classification of primary (direct ligand binding) and secondary (indirect) changes in thermal stability. Overall, this study highlights the value of these assays in the drug development process by affording an unbiased and reliable assessment of compound mechanism of action.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.