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Peer-reviewedCC BY 4.0Communications Chemistry

ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer

Abstract

Knowledge of the targets of therapeutic compounds is vital for understanding their action mechanisms and side effects, but such valuable data is seldom available. The multiple complementary techniques needed for comprehensive target characterization must combine data reliability with sufficient analysis throughput. Here, we leveraged the Proteome Integral Solubility Alteration (PISA) assay to characterize the targets of 67 approved and experimental compounds against two main lung cancer subtypes, which is now provided through the website https://thermotargetminer.serve.scilifelab.se/app/thermotargetminer . Novel target candidates (pro-targets) were found for 77% of the tested molecules. Comparison of the protein solubility shifts in lysate vs. living cells highlighted the targets directly interacting with the compounds. We verified that the drug PEITC exerts cytotoxicity through the inhibition of a pro-target PAFAH1B. As PISA is now joining the arsenal of fast and reliable target characterization techniques, the presented database, ThermoTargetMiner, will become a useful resource in lung cancer research.

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BibTeX
@article{lyu2026thermotargetminer,
  title = {{ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer}},
  author = {Hezheng Lyu and Hassan Gharibi and Bohdana Sokolova and Mücahit Varli and Anna Voiland and Brady Nilsson and Zhaowei Meng and Massimiliano Gaetani and Amir Ata Saei and Roman A. Zubarev},
  journal = {Communications Chemistry},
  year = {2026},
  month = oct,
  doi = {10.1038/s42004-026-02207-z},
  url = {https://www.nature.com/articles/s42004-026-02207-z},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer
AU  - Hezheng Lyu
AU  - Hassan Gharibi
AU  - Bohdana Sokolova
AU  - Mücahit Varli
AU  - Anna Voiland
AU  - Brady Nilsson
AU  - Zhaowei Meng
AU  - Massimiliano Gaetani
AU  - Amir Ata Saei
AU  - Roman A. Zubarev
PY  - 2026
DA  - 2026/10/02
JO  - Communications Chemistry
DO  - 10.1038/s42004-026-02207-z
UR  - https://www.nature.com/articles/s42004-026-02207-z
AB  - Knowledge of the targets of therapeutic compounds is vital for understanding their action mechanisms and side effects, but such valuable data is seldom available. The multiple complementary techniques needed for comprehensive target characterization must combine data reliability with sufficient analysis throughput. Here, we leveraged the Proteome Integral Solubility Alteration (PISA) assay to characterize the targets of 67 approved and experimental compounds against two main lung cancer subtypes, which is now provided through the website https://thermotargetminer.serve.scilifelab.se/app/thermotargetminer . Novel target candidates (pro-targets) were found for 77% of the tested molecules. Comparison of the protein solubility shifts in lysate vs. living cells highlighted the targets directly interacting with the compounds. We verified that the drug PEITC exerts cytotoxicity through the inhibition of a pro-target PAFAH1B. As PISA is now joining the arsenal of fast and reliable target characterization techniques, the presented database, ThermoTargetMiner, will become a useful resource in lung cancer research.
SN  - 2399-3669
ER  -