PXD071495-1

PXD071495 is an original dataset announced via ProteomeXchange.

Title	Discovery of Novel Therapeutic Target STMN1 and Drug Investigation in Familial Adenomatous Polyposis
Description	Familial adenomatous polyposis (FAP), an autosomal dominant disorder that predisposes to colorectal cancer, remains an area of unmet clinical need. This study aimed to develop a novel STMN1-targeting therapy for FAP. Using patient-derived organoids from seven FAP families and RNA sequencing, we identified significant STMN1 upregulation in FAP tissues, correlating with poor prognosis. Through drug repurposing and pharmacophore-based virtual screening of the DrugBank database, we optimized the menadione scaffold to develop novel small-molecule inhibitors. JYL-6 emerged as a leading compound in primary screens using FAP organoids. In Apcmin/+ mice, JYL-6 potently suppressed STMN1 expression and phosphorylation, reduced intestinal polyp number and burden, extended survival, and demonstrated a favorable systemic safety profile. Our results nominate STMN1 as a promising therapeutic target in FAP and highlight JYL-6 as a candidate with substantial translational promise, offering a new strategic direction for FAP treatment.
HostingRepository	iProX
AnnounceDate	2025-12-02
AnnouncementXML	Submission_2025-12-02_18:07:13.261.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuai Wang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-02 18:06:40	ID requested
⏵ 1	2025-12-02 18:07:13	announced

Dataset with its publication pending

submitter keyword: Familial adenomatous polyposis, STMN1 inhibitor, drug repurposing, organoid, JYL-6, targeted therapy

Yingjian Zhang
contact affiliation	Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology; Department of Gastroenterology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
contact email	zhangyingjian@haust.edu.cn
lab head
Shuai Wang
contact affiliation	Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology; Department of Gastroenterology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
contact email	shuaiwanghkd@163.com
dataset submitter

iProX dataset URI