PXD046553

PXD046553 is an original dataset announced via ProteomeXchange.

Title	ABX464 – structure-activity relationship in a model parasitic nematode and target deconvolution
Description	Within the context of our anthelmintic discovery program, we recently identified and evaluated a quinoline derivative, called ABX464 or obefazimod, as a nematocidal candidate; synthesised a series of analogues which were assessed for activity against the free-living model nematode Caenorhabditis elegans; and predicted compound-target relationships by thermal proteome profiling (TPP) and in silico docking. Here, we logically extend(ed) this work and critically evaluate(d) the anthelmintic activity of ABX464 analogues on Haemonchus contortus (barber’s pole worm) – a highly pathogenic nematode of ruminant livestock. First, we tested a series of 44 analogues on H. contortus (larvae and adults) to investigate ABX464’s nematocidal pharmacophore, and identified one compound with greater potency than the parent compound, and also showed moderate activity against a select number of other parasitic nematodes (including Ancylostoma, Heligmosomoides and Strongyloides species). Using TPP and in silico modelling studies, we predicted protein HCON_00074590 (a predicted aldo-keto reductase) as a target candidate for ABX464 in H. contortus. Future work aims to optimise this compound as a nematocidal candidate and investigate its pharmacokinetic properties. Overall, this study presents the first steps towards the development of a new anthelmintic with a novel, distinct mechanism of action.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:28:44.145.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tao Wang
SpeciesList	scientific name: Haemonchus contortus (Barber pole worm); NCBI TaxID: 6289;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-31 19:04:45	ID requested
1	2024-02-06 16:51:19	announced
⏵ 2	2024-10-22 06:28:45	announced	2024-10-22: Updated project metadata.

10.1016/j.ijpddr.2024.100522;

Shanley HT, Taki AC, Nguyen N, Wang T, Byrne JJ, Ang CS, Leeming MG, Nie S, Williamson N, Zheng Y, Young ND, Korhonen PK, Hofmann A, Chang BCH, Wells TNC, H, ä, berli C, Keiser J, Jabbar A, Sleebs BE, Gasser RB, Structure-activity relationship and target investigation of 2-aryl quinolines with nematocidal activity. Int J Parasitol Drugs Drug Resist, 24():100522(2024) [pubmed]

submitter keyword: nematode, LC-MS/MS

Robin Beat Gasser
contact affiliation	Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, Victoria 3010, 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/2024/02/PXD046553

PRIDE project URI

• PRIDE
  1. PXD046553
     1. Label: PRIDE project
     2. Name: ABX464 – structure-activity relationship in a model parasitic nematode and target deconvolution