PXD025020

PXD025020 is an original dataset announced via ProteomeXchange.

Title	A MALDI-TOF assay identifies nilotinib as an inhibitor of inflammation
Description	Inflammatory responses are important in cancer, particularly in the context of monocyte-rich aggressive myeloid neoplasm. We developed a label-free cellular phenotypic drug discovery assay to identify anti-inflammatory drugs in human monocytes derived from acute myeloid leukemia (AML), by quantifying several biological features ionizing from only 2,500 cells using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. A proof-of-concept screening showed that the BCR-ABL inhibitor nilotinib, but not the structurally similar imatinib, blocks inflammatory responses in AML and multiple myeloma. In order to identify the cellular (off-)targets for nilotinib, we performed thermal proteome profiling (TPP) over a range of temperatures and compound concentrations. Unlike imatinib, nilotinib inhibits p38 alpha MAP Kinase (MAPK14) and its downstream signaling pathway. This suppressed the expression of inflammatory cytokines, cell adhesion, and innate immunity markers in activated human monocytes derived from AML. Thus, our study provides a tool for the discovery of new anti-inflammatory drugs, which could potentially contribute to the treatment of inflammation in myeloid neoplasms and other diseases.
HostingRepository	PRIDE
AnnounceDate	2022-09-30
AnnouncementXML	Submission_2022-09-30_08:00:25.011.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Trost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-25 23:39:23	ID requested
⏵ 1	2022-09-30 08:00:25	announced

Mar, í, n-Rubio JL, Peltier-Heap RE, Due, ñ, as ME, Heunis T, Dannoura A, Inns J, Scott J, Simpson AJ, Blair HJ, Heidenreich O, Allan JM, Watt JE, Martin MP, Saxty B, Trost M, A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Assay Identifies Nilotinib as an Inhibitor of Inflammation in Acute Myeloid Leukemia. J Med Chem, 65(18):12014-12030(2022) [pubmed]

submitter keyword: Drug discovery, MALDI-TOF, temperature proteome profiling, inhibitors of inflammation, nilotinib

Prof. Matthias Trost
contact affiliation	Bioscience Institute,Faculty for Medical Sciences at Newcastle University. Newcastle-Upon-Tyne United Kingdom NE24HH
contact email	matthias.trost@ncl.ac.uk
lab head
Matthias Trost
contact affiliation	Newcastle University
contact email	matthias.trost@ncl.ac.uk
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/2022/09/PXD025020

PRIDE project URI

• PRIDE
  1. PXD025020
     1. Label: PRIDE project
     2. Name: A MALDI-TOF assay identifies nilotinib as an inhibitor of inflammation