1. Tracking cancer drugs in living cells by thermal profiling of the proteome
- Author
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Rebecca Dovega, Dirk Eberhard, Marcus Bantscheff, Maria Fälth Savitski, Bernhard Kuster, Holger Franken, Thilo Werner, Susan Klaeger, Pär Nordlund, Gerard Drewes, Mikhail M. Savitski, Rozbeh Jafari, Daniel Martinez Molina, and Friedrich B M Reinhard
- Subjects
Proteomics ,Thermal shift assay ,Protein Denaturation ,Hot Temperature ,Proteome ,Antineoplastic Agents ,Plasma protein binding ,Pharmacology ,Ligands ,Adapter molecule crk ,medicine ,Staurosporine ,Humans ,Adenosine Triphosphatases ,Multidisciplinary ,biology ,Protein Stability ,Ferrochelatase ,Cell biology ,CRKL ,Dasatinib ,biology.protein ,K562 Cells ,medicine.drug ,Protein Binding - Abstract
Mapping human drug targets in the cell To understand both the beneficial and the side effects of a drug, one would need to know its full binding profile to all cellular proteins. Savitski et al. take significant steps toward meeting this daunting challenge. They monitored the unfolding or “melting” of over 7000 human proteins and measured how small-molecule binding changes individual melting profiles. As a proof of principle, over 50 targets were identified for an inhibitor known to bind a broad spectrum of kinases. Two cancer drugs, vemurafib and Alectinib, are known to have a side effect of photosensitivity. The thermal profiling approach identified drug-protein interactions responsible for these side effects. Science , this issue 10.1126/science.1255784
- Published
- 2014