PXD004541

PXD004541 is an original dataset announced via ProteomeXchange.

Title	CETSA proteomics to investigate drug binding in BJ Ras Sv40 cells treated with MTH1 inhibitors.
Description	Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidative nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Here, we demonstrate that these recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We further describe a new MTH1 inhibitor TH1579, an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to test the MTH1 inhibitor concept. Cellular thermal shift assay (CETSA) combined with basic reversed phase (bRP) separation and LC-MS was used to study drug binding in BJ Ras Sv40 cells treated with the MTH1 inhibitor TH1579.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:31:18.690.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rui Branca
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-07-11 02:31:11	ID requested
1	2016-12-22 05:34:13	announced
2	2017-10-24 03:16:37	announced	Updated project metadata.
⏵ 3	2024-10-22 04:31:26	announced	2024-10-22: Updated project metadata.

Warpman Berglund U, Sanjiv K, Gad H, Kalder, é, n C, Koolmeister T, Pham T, Gokturk C, Jafari R, Maddalo G, Seashore-Ludlow B, Chernobrovkin A, Manoilov A, Pateras IS, Rasti A, Jemth AS, Alml, ö, f I, Loseva O, Visnes T, Einarsdottir BO, Gaugaz FZ, Saleh A, Platzack B, Wallner OA, Vallin KS, Henriksson M, Wakchaure P, Borhade S, Herr P, Kallberg Y, Baranczewski P, Homan EJ, Wiita E, Nagpal V, Meijer T, Schipper N, Rudd SG, Br, ä, utigam L, Lindqvist A, Filppula A, Lee TC, Artursson P, Nilsson JA, Gorgoulis VG, Lehti, ö J, Zubarev RA, Scobie M, Helleday T, Validation and development of MTH1 inhibitors for treatment of cancer. Ann Oncol, 27(12):2275-2283(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: proteomics, LC-MS, BJ Ras Sv40 cells, CETSA,human

Janne Lehtiö
contact affiliation	Dept. Oncology Pathology, Karolinska Institutet, and ScilifeLab, Stockholm, Sweden
contact email	janne.lehtio@ki.se
lab head
Rui Branca
contact affiliation	Clinical Proteomics Unit, Dep. of Oncology-Pathology
contact email	rui.mamede-branca@ki.se
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/2016/12/PXD004541

PRIDE project URI

• PRIDE
  1. PXD004541
     1. Label: PRIDE project
     2. Name: CETSA proteomics to investigate drug binding in BJ Ras Sv40 cells treated with MTH1 inhibitors.