PXD057229

PXD057229 is an original dataset announced via ProteomeXchange.

Title	A cereblon-based (CRBN) glue degrader of NEK7 regulates NLRP3 inflammasome in a context-dependent manner
Description	Aberrant NLRP3 inflammasome activation is linked to many inflammatory diseases, driving the search for therapeutics inhibiting this pathway. NEK7 is proposed to mediate NLRP3 inflammasome assembly and activation by bridging adjacent NLRP3 subunits. Hence, reduction of NEK7 protein may block NLRP3 activation. We identified NK7-902, a potent and selective CRBN glue degrader of NEK7. NK7-902 degraded NEK7 in human immune cells and whole blood. However, full NEK7 degradation completely blocked NLRP3-dependent IL-1β release in vitro only in certain donors and experimental conditions. Unlike most CRBN glue degraders, NK7-902 effectively degraded NEK7 in murine cells and inhibited IL-1β release in mouse in vivo. By contrast, oral administration of NK7-902 in cynomolgus monkey caused long-lasting NEK7 degradation but only transiently blocked IL-1β in blood. These findings suggest NEK7 contributes to but is not absolutely required for NLRP3 activation in monkeys and humans.
HostingRepository	PRIDE
AnnounceDate	2025-06-18
AnnouncementXML	Submission_2025-06-18_02:44:47.900.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD057229
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andreas Hofmann
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-27 14:59:11	ID requested
⏵ 1	2025-06-18 02:44:48	announced

10.6019/PXD057229;

submitter keyword: molecular glue degrader, inflammation,NEK7, NLRP3 inflammasome, CRBN

Andreas Josef
contact affiliation	Novartis Biomedical Research
contact email	andreas.hofmann@novartis.com
lab head
Andreas Hofmann
contact affiliation	NIBR
contact email	andreas.hofmann@novartis.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/2025/06/PXD057229

PRIDE project URI

• PRIDE
  1. PXD057229
     1. Label: PRIDE project
     2. Name: A cereblon-based (CRBN) glue degrader of NEK7 regulates NLRP3 inflammasome in a context-dependent manner