PXD025822-1

PXD025822 is an original dataset announced via ProteomeXchange.

Title	The Phenyl Indole p97 inhibitor, UPCDC-30245, blocks endo-lysosomal degradation and coronavirus entry to host cells
Description	Different modes of action small molecule inhibitors provide versatile tools for investigation of biology and development of therapeutics. However, to evaluate their exact mechanism of actions remains to be a challenging tas. We have identified two classes of p97 inhibitors, ATP competitive and allosteric inhibitors. We initially showed that the allosteric phenyl indole p97 inhibitor, UPCDC-30245, does not affect on two well-known cellular functions of p97, Endoplasmic-reticulum-associated protein degradation (EARD) and unfolded protein response (UPR) pathway dramatically, instead strongly increases the lapidated form of microtubule-associated proteins 1A/1B light chain 3B (LC3-II). To evaluate the molecular mechanism of UPCDC-30245, we performed proteomic analysis of UPCDC-30245 treated cells. Our results revealed UPCDC-30245 blocks endo-lysosomal degradation via inhibiting the formation of early endosome and reducing the acidity of lysosome and this is aa potential off-target effect. More importantly, we demonstrated UPCDC-30245 exhibits promising ntiviral effects via blocking virus entry and this could be due to both on-target and off-target effect.
HostingRepository	PRIDE
AnnounceDate	2022-05-25
AnnouncementXML	Submission_2022-05-25_07:10:04.982.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025822
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Feng Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-05 22:46:57	ID requested
⏵ 1	2022-05-25 07:10:05	announced

Wang F, Li S, Cheng KW, Rosencrans WM, Chou TF, The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation. Pharmaceuticals (Basel), 15(2):(2022) [pubmed]

ProteomeXchange project tag: Sars-cov-2, Cancer (B/D-HPP), Covid-19, Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: p97 inhibitor

proteomic

anti-virus

Tsui-Fen Chou
contact affiliation	BBE, Caltech
contact email	tfchou@caltech.edu
lab head
Feng Wang
contact affiliation	Caltech
contact email	fengwang@caltech.edu
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/2022/04/PXD025822

PRIDE project URI

• PRIDE
  1. PXD025822
     1. Label: PRIDE project
     2. Name: The Phenyl Indole p97 inhibitor, UPCDC-30245, blocks endo-lysosomal degradation and coronavirus entry to host cells