PXD030140

PXD030140 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Methotrexate-based PROTACs as DHFR chemical probes
Description	Methotrexate (MTX) is a potent inhibitor of dihydrofolate reductase (DHFR), where is it used as both an antineoplastic and an immunosuppressant. Mechanisms of MTX resistance in cancers include MTX polyglutamylation and upregulation of DHFR. A series of MTX-based PROteolysis TArgeting Chimeras (PROTACs) were designed to selectively degrade human DFHR. These on-target, cell-active PROTACs show proteosome- and E3 ligase-dependent DHFR degradation, selective degradation of DHFR by proteomics, and interpretable structure-activity relationships. Importantly, these PROTACs produced distinct, less-lethal phenotypes compared to MTX, indicating these compounds can complement conventional DFHR enzymatic inhibitors as tool compounds. This chemical probe set, composed of the PROTAC (Diruotrexate), its ester pro-drug (Diruotrexate-ester) and negative control analogs (Diruotrexate-IA1, -IA2), should serve as useful tools for studying one-carbon biochemistry.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:00:25.027.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD030140
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dingyin Tao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-02 08:20:51	ID requested
⏵ 1	2025-05-06 09:00:25	announced

Publication List

10.6019/PXD030140;
Rana S, Dranchak P, Dahlin JL, Lamy L, Li W, Oliphant E, Shrimp JH, Rajacharya GH, Tharakan R, Holland DO, Whitten AS, Wilson KM, Singh PK, Durum SK, Tao D, Rai G, Inglese J, Methotrexate-based PROTACs as DHFR-specific chemical probes. Cell Chem Biol, 31(2):221-233.e14(2024) [pubmed]
10.1016/j.chembiol.2023.09.014;

10.6019/PXD030140;

Rana S, Dranchak P, Dahlin JL, Lamy L, Li W, Oliphant E, Shrimp JH, Rajacharya GH, Tharakan R, Holland DO, Whitten AS, Wilson KM, Singh PK, Durum SK, Tao D, Rai G, Inglese J, Methotrexate-based PROTACs as DHFR-specific chemical probes. Cell Chem Biol, 31(2):221-233.e14(2024) [pubmed]

10.1016/j.chembiol.2023.09.014;

Keyword List

submitter keyword: DHFR, targeted protein degradation, methotrexate,chemical probe, PROTAC, one carbon metabolism

submitter keyword: DHFR, targeted protein degradation, methotrexate,chemical probe, PROTAC, one carbon metabolism

Contact List

Dingyin Tao
contact affiliation	National Center for Advancing Translational Sciences (NCATS) NIH
contact email	dingyin.tao@nih.gov
lab head
Dingyin Tao
contact affiliation	National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS)
contact email	dingyin.tao@nih.gov
dataset submitter

Full Dataset Link List

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PRIDE project URI

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/2025/05/PXD030140

PRIDE project URI

Repository Record List

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