PXD042930

PXD042930 is an original dataset announced via ProteomeXchange.

Title	Assessment of the nematocidal potency of ABX464 analogues and target deconvolution in Caenorhabditis elegans by thermal proteome profiling
Description	Global challenges with anthelmintic failure and resistance development lends impetus to the development of new nematocides (anthelmintics) with novel mechanism(s) of action. The free-living nematode Caenorhabditis elegans is as an important model organism used for drug discovery and a powerful tool for anthelmintic screening, evaluation and target deconvolution. Previously, we conducted a whole-organism phenotypic screen of the ‘Pandemic Response Box’ (from Medicines for Malaria Venture, MMV) and identified a hit compound, called ABX464, with activity against C. elegans. Here, we explored this nematocidal pharmacophore on C. elegans, and then tested a series of 46 analogues for human hepatoma (HepG2) toxicity, revealing five compounds whose potency was similar or greater than that of ABX464. Subsequently, we employed thermal proteome profiling (TPP), protein structure prediction and an in silico docking algorithm to identify prime ABX464-target candidates. Taken together, the findings from this study contribute significantly to the early-stage drug discovery of a new nematocide based on ABX464. Future work is aimed at validating the ABX464-protein interactions identified here, and at assessing of ABX464 and associated analogues against a panel of parasitic nematodes, towards the development of a new anthelmintic with a novel mechanism of action.
HostingRepository	PRIDE
AnnounceDate	2024-01-29
AnnouncementXML	Submission_2024-01-28_21:06:54.837.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tao Wang
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-12 20:59:54	ID requested
⏵ 1	2024-01-28 21:06:55	announced

10.1016/J.BMC.2023.117540;

submitter keyword: thermal proteome profiling

LC-MS/MS

Caenorhabditis elegans

Robin Beat Gasser
contact affiliation	Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Victoria, Australia
contact email	robinbg@unimelb.edu.au
lab head
Tao Wang
contact affiliation	The University of Melbourne
contact email	tao.wang1@unimelb.edu.au
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/2024/01/PXD042930

PRIDE project URI

• PRIDE
  1. PXD042930
     1. Label: PRIDE project
     2. Name: Assessment of the nematocidal potency of ABX464 analogues and target deconvolution in Caenorhabditis elegans by thermal proteome profiling