Journal Article DKFZ-2023-00554

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Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.

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2023
Moses King Cambridge, Mass.

Science 380(6640), 93-101 () [10.1126/science.ade3925]
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Abstract: Although most cancer drugs modulate the activities of cellular pathways by changing post-translational modifications (PTMs), surprisingly little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. Here, we introduce a proteomic assay termed decryptM that quantifies drug-PTM modulation for thousands of PTMs in cells to shed light on target engagement and drug mechanism of action (MoA). Examples range from detecting DNA damage by chemotherapeutics, to identifying drug-specific PTM signatures of kinase inhibitors, to demonstrating that rituximab kills CD20-positive B-cells by over-activating B cell receptor signaling. DecryptM profiling of 31 cancer drugs in 13 cell lines demonstrates the broad applicability of the approach. The resulting 1.8 million dose-response curves are provided as an interactive molecular resource in ProteomicsDB.

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Note: 2023 Apr 7;380(6640):93-101

Contributing Institute(s):
  1. DKTK MU LMU zentral (MU01)
  2. DKTK ED ES zentral (ED01)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023
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Medline ; BIOSIS Previews ; Biological Abstracts ; Biological Abstracts ; Chemical Reactions ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Essential Science Indicators ; IF >= 50 ; Index Chemicus ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record
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 Record created 2023-03-20, last modified 2024-02-29



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