Strategy to follow-up and validate hits from phenotypic screening by cellular thermal shift assay coupled with mass spectrometry (CETSA-MS)
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Publikationsdatum
2025
Typ der Arbeit
Master
Studiengang
Life Science MSLS
Typ
11 - Studentische Arbeit
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Hochschule für Life Sciences FHNW
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Novartis
Zusammenfassung
Phenotypic screening is a widely used approach in drug discovery to identify small molecules exhibiting desirable effects in disease models. However, a significant challenge is to determine the targets of these phenotypic screen hits. This leads to the need of efficient target deconvolution strategies to understand their mode of action and off-target effects, which would accelerate drug development in addition [1, 2].
One recent technology used for target deconvolution is the cellular thermal shift assay (CETSA). This assay works on the principle that heating lead to protein denaturation and denatured proteins start to aggregate, what decreases the solubility. Combined with the knowledge that the denaturation temperature (melting temperature) of a protein is shifted upon compound binding, the interaction can be investigated by quantifying the soluble part of a sample at different temperatures [3].
Now, if the CETSA technique is connected to mass spectrometry (MS) bottom-up proteomics, it enables the investigation of interactions between a compound and thousands of proteins in one experiment. For this reason, CETSA-MS is a powerful and efficient assay for target deconvolution [4]
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Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
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Open Access-Status
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Zitation
Bürgler, S. (2025). Strategy to follow-up and validate hits from phenotypic screening by cellular thermal shift assay coupled with mass spectrometry (CETSA-MS) [Hochschule für Life Sciences FHNW]. https://doi.org/10.26041/fhnw-15117