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PXD018574

PXD018574 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 6
DescriptionMass spectrometry-based discovery proteomics is an essential tool for the proximal read-out of cellular drug action. Here, we used a robust proteomic workflow to rapidly and systematically profile the proteomes of five cell lines in response to > 50 drugs. We found that aggregating millions of quantitative protein-drug associations substantially improved the mechanism of action (MoA) deconvolution of single compounds. For example, MoA specificity increased after removal of proteins which frequently responded to drugs and the aggregation of proteome changes across multiple cell lines resolved compound effects on proteostasis. These characteristics were further leveraged to demonstrate efficient target identification of protein degraders. Moreover, we followed up on selected proteomic findings and showed that the inhibition of mitochondrial function is an off-target mechanism of the clinical MEK inhibitor PD184352 and that Ceritinib, an FDA approved drug in lung cancer, modulates autophagy. Overall, this study demonstrates that large-scale proteome perturbation profiling can be a useful addition to the drug discovery toolbox.
HostingRepositoryPRIDE
AnnounceDate2020-08-17
AnnouncementXMLSubmission_2020-09-28_00:28:59.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBenjamin Ruprecht
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-15 03:47:06ID requested
12020-08-16 22:39:35announced
22020-09-28 00:29:01announced2020-09-28: Updated publication reference for PubMed record(s): 32690943.
Publication List
Ruprecht B, Di Bernardo J, Wang Z, Mo X, Ursu O, Christopher M, Fernandez RB, Zheng L, Dill BD, Wang H, Xu Y, Liaw A, Mortison JD, Siriwardana N, Andresen B, Glick M, Tata JR, Kutilek V, Cornella-Taracido I, Chi A, A mass spectrometry-based proteome map of drug action in lung cancer cell lines. Nat Chem Biol, 16(10):1111-1119(2020) [pubmed]
Keyword List
submitter keyword: Drug discovery, Mass spectrometry, Proteomics, Perturbation profiling
Contact List
An Chi
contact affiliationMerck
contact emailAn_Chi@merck.com
lab head
Benjamin Ruprecht
contact affiliationMerck
contact emailBenjamin.Ruprecht@merck.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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