PXD012805

PXD012805 is an original dataset announced via ProteomeXchange.

Title	Diverse Compounds from Pleuromutilin Lead to a Thioredoxin Inhibitor and Inducer of Ferroptosis
Description	The chemical diversification of natural products provides a robust and general method for creation of stereochemically complex and structurally diverse small molecules. The resulting compounds have physicochemical traits different from those in most screening collections, and as such are a rich source for biological discovery. Herein, we subject the terpene natural product pleuromutilin to reaction sequences focused on creating ring system diversity in few synthetic steps. This effort resulted in the synthesis of multiple compounds with previously unreported ring systems, providing a set of novel structurally diverse and highly complex compounds suitable for screening in a variety of different settings. Biological evaluation of these compounds identified the novel compound ferroptocide, a compound that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR KO studies reveal that ferroptocide is an inhibitor of thioredoxin, a key component of thioredoxin antioxidant system in the cell. Ferroptocide shows the ability to positively modulate the immune system in a murine model of breast cancer and will be a useful tool to study the ability of pro-ferroptotic agents to synergize with the immune system for treatment of cancer.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_13:23:13.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eranthie Weerapana
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-20 07:59:30	ID requested
⏵ 1	2020-05-26 13:23:14	announced

Llabani E, Hicklin RW, Lee HY, Motika SE, Crawford LA, Weerapana E, Hergenrother PJ, Diverse compounds from pleuromutilin lead to a thioredoxin inhibitor and inducer of ferroptosis. Nat Chem, 11(6):521-532(2019) [pubmed]

submitter keyword: thioredoxin, ferroptosis

Eranthie Weerapana
contact affiliation	Department of Chemistry, Boston College, Chestnut Hill, MA
contact email	eranthie@bc.edu
lab head
Eranthie Weerapana
contact affiliation	Boston College
contact email	eranthie@bc.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/2020/05/PXD012805

PRIDE project URI

• PRIDE
  1. PXD012805
     1. Label: PRIDE project
     2. Name: Diverse Compounds from Pleuromutilin Lead to a Thioredoxin Inhibitor and Inducer of Ferroptosis