PXD064642

PXD064642 is an original dataset announced via ProteomeXchange.

Title	Low Density Lipoprotein Receptor Targeting Chimeras for Membrane Protein Degradation and Enhanced Drug Delivery
Description	Antibody-based therapeutics encompass diverse modalities for targeting tumor cells, among which antibody-drug conjugates (ADCs) and extracellular targeted protein degradation (eTPD) specifically depend on efficient lysosomal trafficking for activity. However, many tumor antigens exhibit poor internalization, limiting ADC effectiveness. To address this, we developed low-density lipoprotein receptor-targeting chimeras (LIPTACs), leveraging the constitutive endocytic and recycling activity of the low-density LDLR to enhance lysosomal delivery. LIPTACs enable robust degradation of diverse extracellular membrane proteins, including neo-epitopes on RAS-driven cancer cells. Moreover, by coupling LIPTACs with cytotoxic payloads to generate degrader-drug conjugates, we achieve superior intracellular delivery and enhanced cytotoxicity compared to conventional ADCs.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-09_16:18:48.994.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kaitlin Schaefer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	6x(13)C labeled residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Bruker Daltonics instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-04 12:42:06	ID requested
⏵ 1	2025-11-09 16:18:50	announced

Zhao F, Wu Y, Schaefer K, Zhang Y, Miao K, Yao Z, Ganjave SD, Kumru K, Peters-Clarke TM, Inague A, Olzmann JA, Leung KK, Wells JA, Hijacking Extracellular Targeted Protein Degrader-Drug Conjugates for Enhanced Drug Delivery. J Am Chem Soc, 147(43):39912-39925(2025) [pubmed]

10.1021/jacs.5c15047;

ProteomeXchange project tag: Antibodies (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Antibody based degradation

James A Wells
contact affiliation	Pharmaceutical Chemistry, UCSF
contact email	jim.wells@ucsf.edu
lab head
Kaitlin Schaefer
contact affiliation	University of California, San Francisco
contact email	kaitlin.schaefer@ucsf.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/2025/11/PXD064642

PRIDE project URI

• PRIDE
  1. PXD064642
     1. Label: PRIDE project
     2. Name: Low Density Lipoprotein Receptor Targeting Chimeras for Membrane Protein Degradation and Enhanced Drug Delivery