PXD070302-1

PXD070302 is an original dataset announced via ProteomeXchange.

Title	Natural product target identification of wheldone as a KIF11 inhibitor in ovarian cancer using the DiffPOP (Differential Protein Precipitation) method
Description	Wheldone, a fungal metabolite, was identified as a cytotoxic compound in high-grade serous ovarian cancer (HGSOC). Wheldone triggered caspase 3/7–dependent apoptosis and reduced migration, invasion, and spheroid growth. Wheldone was also capable of triggering apoptosis in chemoresistant HGSOC models. Wheldone caused significant downregulation of HNRNPD expression, a DNA repair protein, and increased DNA damage that could be blocked by N-acetyl-L-cysteine. In vivo, wheldone displayed minimal toxicity but was rapidly cleared from circulation, despite in vitro metabolic stability. Wheldone treatment in vivo did not demonstrate significant reduction in tumor burden. Therefore, in order to overcome these liabilities, it was necessary to find the protein target of wheldone so that modifications can be made to improve the drug-like characteristics of the compound. Using the drug-target interaction proteomics method, DiffPOP (differential precipitation of proteins), wheldone was found to act as an inhibitor of KIF11, a motor protein essential for mitotic spindle formation. An ATPase biochemical cell-free assay confirmed direct binding and functional inhibition of KIF11. Wheldone resulted in G2/M arrest and downstream regulation of mitotic proteins such as TPX2, AURKA, and phospho-histone H3. Proteomics analysis after treatment of wheldone in four different HGSOC cancer cell lines all supported changes consistent with mitotic spindle assembly disruption. Further, KIF11 was one of only 13 proteins upregulated in all four cell lines treated. Overall, wheldone represents a promising lead compound for targeting KIF11 in chemoresistant ovarian cancer, with future studies needed to improve its pharmacokinetics and delivery.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_20:13:29.250.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dany Pechalrieu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-04 08:28:59	ID requested
⏵ 1	2026-05-24 20:13:30	announced

10.1016/j.mcpro.2026.101558;

Khin M, Saldana AC, Rangel-Grimaldo M, Raja HA, Abegg D, Ekiert J, Liu C, Misra S, Ratia K, Adibekian A, Gao Y, Kulp SK, Coss CC, Oberlies NH, Burdette JE, Natural Product Target Identification of Wheldone, a Fungal Metabolite, as a KIF11 Inhibitor in Ovarian Cancer Using the DiffPOP (Differential Protein Precipitation) Method. Mol Cell Proteomics, 25(5):101558(2026) [pubmed]

submitter keyword: Ovarian Cancer, Cancer Biology, Proteomics, target identification, Natural Products

Alexander Adibekian
contact affiliation	Department of Chemistry, University of Illinois Chicago, Chicago, USA
contact email	aadibeki@uic.edu
lab head
Dany Pechalrieu
contact affiliation	University of Illinois Chicago
contact email	dpechalr@uic.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070302
     1. Label: PRIDE project
     2. Name: Natural product target identification of wheldone as a KIF11 inhibitor in ovarian cancer using the DiffPOP (Differential Protein Precipitation) method