PXD078921-1

PXD078921 is an original dataset announced via ProteomeXchange.

Title	A Covalent PFKL Activator Suppresses Tumor Growth
Description	Glycolysis fuels vital cellular functions and its dysregulation is implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, presents a key vulnerability for developing targeted anticancer agents but remains challenging due to metabolic heterogeneity and resistance. Here, we developed a first-in-class covalent phosphofructokinase-1 liver type (PFKL) activator that couples glycolytic activation with delivery of a cytotoxic carnitine palmitoyltransferase 2 (CPT2)-targeting payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate (EDC) site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL while concomitantly releasing a CPT2-selective inhibitor to destabilize cell metabolism. We introduce EDCs as a new delivery mechanism analogous to antibody-drug conjugates but differentiated by selective covalent targeting of intracellular proteins.
HostingRepository	PRIDE
AnnounceDate	2026-06-18
AnnouncementXML	Submission_2026-06-17_16:16:24.134.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ku-Lung Hsu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-27 11:05:48	ID requested
⏵ 1	2026-06-17 16:16:24	announced

Dataset with its publication pending

submitter keyword: PFKL, EDC, Covalent activator, Tumor Supression, Glycolysis

Ku-Lung Hsu
contact affiliation	The University of Texas at Austin
contact email	ken.hsu@austin.utexas.edu
lab head
Ku-Lung Hsu
contact affiliation	The University of Texas at Austin
contact email	ken.hsu@austin.utexas.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/2026/06/PXD078921

PRIDE project URI

• PRIDE
  1. PXD078921
     1. Label: PRIDE project
     2. Name: A Covalent PFKL Activator Suppresses Tumor Growth