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

Lyu, H.; Gharibi, H.; Sokolova, B.; Voiland, A.; Nilsson, B.; Meng, Z.; Gaetani, M.; Saei, A. A.; Zubarev, R.

2024-08-06 biochemistry
10.1101/2024.08.06.606599 bioRxiv
Show 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 comprehensively characterize the targets of 67 approved drugs and candidate compounds against lung cancer. The analysis was performed on two cell lines representing different lung cancer phenotypes and novel targets for 77% of the tested molecules were found. Comparison of the protein solubility shifts in lysate vs. living cells highlighted the targets directly interacting with the compounds. As PISA analysis 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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