PXD070862

PXD070862 is an original dataset announced via ProteomeXchange.

Title	Application of folding stability-based proteomics to profile cancer drug
Description	Covalent inhibitors offer powerful therapeutic advantages but require comprehensive profiling to define their on- and off-target activities. Here, we apply two stability-based proteomic methods, SPROX and TPP, to characterize protein targets of the KRASG12C inhibitor ARS-1620 in H358 cell lysate. Both methods identified ligand-induced protein stability shifts, collectively recovering the known on-target KRAS as well as multiple off-targets. Comparative analyses with ABPP and pull-down datasets highlighted ALDH1A3 as a reproducible off-target. Bottom-up proteomics mapped Cys314 as the major ARS-1620 modification site on ALDH1A3, and enzymatic assays confirmed dose-dependent inhibition. Covalent docking supported a favorable binding pose within the retinal-binding pocket. Together, these findings demonstrate that stability-based proteomics provides an effective, derivatization-free strategy for covalent drug target identification.
HostingRepository	PRIDE
AnnounceDate	2026-05-08
AnnouncementXML	Submission_2026-05-07_17:30:41.653.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	You Zou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; Oxidation
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-17 17:35:54	ID requested
⏵ 1	2026-05-07 17:30:43	announced

Dataset with its publication pending

submitter keyword: None

Michael C.
contact affiliation	Professor & Chair Chemistry Department Duke University
contact email	michael.c.fitzgerald@duke.edu
lab head
You Zou
contact affiliation	Duke University
contact email	yz785@duke.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/2026/05/PXD070862

PRIDE project URI

• PRIDE
  1. PXD070862
     1. Label: PRIDE project
     2. Name: Application of folding stability-based proteomics to profile cancer drug