PXD024913-1

PXD024913 is an original dataset announced via ProteomeXchange.

Title	Chemical proteomics identifies a novel off-target protein of small molecule NLRP3 inflammasome inhibitor MCC950
Description	Inhibition of inflammasome and pyroptotic pathways are promising strategies for clinical treatment of autoimmune and inflammatory disorders. MCC950, a potent inhibitor of the NLR-family inflammasome pyrin domain-containing 3 (NLRP3) protein, has shown encouraging results in animal models for a range of conditions; however, little is known about its off-target effects. We have designed, synthesized and applied a novel photoaffinity alkyne-tagged probe for MCC950 which shows direct engagement with NLRP3 and inhibition of inflammasome activation in macrophages. Affinity-based chemical proteomics in live macrophages identified several potential off-targets, and independent cellular thermal proteomic profiling revealed stabilization of these by MCC950. This is the results of the affinity-based proteomics.
HostingRepository	PRIDE
AnnounceDate	2021-05-17
AnnouncementXML	Submission_2021-05-16_23:01:37.228.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cassandra Kennedy
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-22 04:36:52	ID requested
⏵ 1	2021-05-16 23:01:37	announced

Dataset with its publication pending

submitter keyword: Human, THP1, MCC950, LC-MS/MS

Edward W Tate
contact affiliation	Department of Chemistry, Imperial College London, UK
contact email	e.tate@imperial.ac.uk
lab head
Cassandra Kennedy
contact affiliation	Imperial College London
contact email	c.kennedy16@imperial.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024913
     1. Label: PRIDE project
     2. Name: Chemical proteomics identifies a novel off-target protein of small molecule NLRP3 inflammasome inhibitor MCC950