PXD037895-1

PXD037895 is an original dataset announced via ProteomeXchange.

Title	A Selective Small-Molecule STAT5 PROTAC Degrader Capable of Achieving Tumor Regression In Vivo
Description	The signal transducer and activator of transcription 5 (STAT5) is an attractive therapeutic target but successful targeting of STAT5 has proved to be difficult. We report herein the development of AK-2292 as a first, potent and selective small-molecule degrader of both STAT5A and STAT5B isoforms. AK-2292 induces degradation of STAT5A/B proteins with an outstanding selectivity over all other STAT proteins and >6,000 non-STAT proteins, leading to selective inhibition of STAT5 activity in cells. AK-2292 effectively induces STAT5 depletion in normal mouse tissues and human chronic myeloid leukemia (CML) xenograft tissues and achieves tumor regression in two CML xenograft mouse models at well-tolerated dose-schedules. AK-2292 is not only a powerful research tool with which to investigate the biology of STAT5 and therapeutic potential of selective STAT5 protein depletion and inhibition in vitro and in vivo, but also a promising lead compound toward ultimate development of a STAT5-targeted therapy.
HostingRepository	PRIDE
AnnounceDate	2023-01-25
AnnouncementXML	Submission_2023-01-25_09:02:18.180.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Longchuan Bai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-03 04:06:32	ID requested
⏵ 1	2023-01-25 09:02:18	announced

Dataset with its publication pending

submitter keyword: TMT proteomics,STAT5, PROTAC

ShaomengWang
contact affiliation	2Departments of Internal Medicine, University of Michigan, Ann Arbor MI 48109, USA.
contact email	shaomeng@umich.edu
lab head
Longchuan Bai
contact affiliation	University of Michigan
contact email	lbai@med.umich.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/2023/01/PXD037895

PRIDE project URI

• PRIDE
  1. PXD037895
     1. Label: PRIDE project
     2. Name: A Selective Small-Molecule STAT5 PROTAC Degrader Capable of Achieving Tumor Regression In Vivo