PXD018572

PXD018572 is an original dataset announced via ProteomeXchange.

Title	A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 4
Description	Mass 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:10:50.373.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Benjamin Ruprecht
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-15 03:46:07	ID requested
1	2020-08-16 22:30:12	announced
2	2020-09-28 00:28:58	announced	2020-09-28: Updated publication reference for PubMed record(s): 32690943.
⏵ 3	2024-10-22 05:10:56	announced	2024-10-22: Updated project metadata.

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]

10.1038/s41589-020-0572-3;

submitter keyword: Mass spectrometry,Drug discovery, Proteomics, Perturbation profiling

An Chi
contact affiliation	Merck
contact email	An_Chi@merck.com
lab head
Benjamin Ruprecht
contact affiliation	Merck
contact email	Benjamin.Ruprecht@merck.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/08/PXD018572

PRIDE project URI

• PRIDE
  1. PXD018572
     1. Label: PRIDE project
     2. Name: A mass spectrometry-based proteome map of drug action in lung cancer cell lines Part 4