Science· 2014Q1
Tracking cancer drugs in living cells by thermal profiling of the proteome
- 1,224citations
- Q1SCImago
- 2014year
Short summary
Thermal proteome profiling (TPP) using mass spectrometry can now monitor over 7000 proteins in live cells to reveal drug-target interactions and downstream effects.
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Key points
- Thermal proteome profiling (TPP) was used to determine thermal profiles for over 7000 proteins in human cells.
- TPP identified >50 targets for the kinase inhibitor staurosporine.
- Ferrochelatase was identified as a target of kinase inhibitors, linked to phototoxicity of vemurafenib and alectinib.
- Dasatinib induced thermal shifts in BCR-ABL pathway proteins (e.g., CRK/CRKL) in live cells.
AI-generated from the title and abstract; the full text is not read.
Abstract
The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles delineated more than 50 targets for the kinase inhibitor staurosporine. We identified the heme biosynthesis enzyme ferrochelatase as a target of kinase inhibitors and suggest that its inhibition causes the phototoxicity observed with vemurafenib and alectinib. Thermal shifts were also observed for downstream effectors of drug treatment. In live cells, dasatinib induced shifts in BCR-ABL pathway proteins, including CRK/CRKL. Thermal proteome profiling provides an unbiased measure of drug-target engagement and facilitates identification of markers for drug efficacy and toxicity.
The authors' abstract, as published at the source. Science, 2014 · DOI ↗
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Field: Spectroscopy
SpectroscopyChemistry