PXD057157-1

PXD057157 is an original dataset announced via ProteomeXchange.

Title	Solvent-Induced partial Cellular Fixation Approach enables systematic identification of drug targets and temporal progression of downstream biochemical pathways in living cells
Description	In this study, we introduce a novel approach, the Solvent-Induced Partial Cellular Fixation Approach (SICFA), to monitor drug targets and the temporal progression of downstream biochemical pathways in living cells. We observed that proteins in living cells undergo unfolding and aggregation when exposed to increasing concentrations of solvent-based fixatives, a process modifiable by molecular interactions and intracellular dynamics. Combined with quantitative proteomics, SICFA can precisely detect the effects of drugs on the stability of target and downstream effector proteins. As proof of concept, the intracellular targets and downstream effector proteins of several drugs were identified. Additionally, the IsoSolvent Dose-Response (ISDR)-SICFA workflow was developed to quantify drug-target binding potency within cells. To distinguish between direct drug targets and downstream biochemical pathways, time-dependent experiments were integrated with SICFA, systematically identifying the molecular initiation, intermediate, and outcome events triggered by 5-fluorouracil (5-FU). Notably, SICFA revealed that the early stages of 5-FU treatment primarily impact RNA post-transcriptional modification and ribosome biogenesis pathways. Unlike protein expression data, the stability data provided by SICFA offers higher sensitivity, filling the gap in understanding early biochemical events during drug treatment.
HostingRepository	PRIDE
AnnounceDate	2025-10-15
AnnouncementXML	Submission_2025-10-15_15:00:23.718.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ting Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-24 10:18:00	ID requested
⏵ 1	2025-10-15 15:00:24	announced

Dataset with its publication pending

submitter keyword: Proteomics

Protein Stability

Drug Target Identification

Drug Binding Potency

Downstream Effector Proteins

Living Cells Analysis

Mingliang Ye
contact affiliation	Dalian Institute of Chemical Physics, CAS
contact email	mingliang@dicp.ac.cn
lab head
Ting Yu
contact affiliation	Dalian Institute of Chemical Physics, CAS
contact email	yuting@dicp.ac.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057157
     1. Label: PRIDE project
     2. Name: Solvent-Induced partial Cellular Fixation Approach enables systematic identification of drug targets and temporal progression of downstream biochemical pathways in living cells