PXD009188

PXD009188 is an original dataset announced via ProteomeXchange.

Title	Single methyl group positioning opens new chemical space for EPH receptor kinase inhibition
Description	EPHrin receptors (EPH) are transmembrane receptor tyrosine kinases. Their extracellular domains bind specifically to ephrin A/B ligands, and this binding modulates the intracellular kinase activity. EPHs are key players in bidirectional intercellular signalling, controlling cell morphology, adhesion and migration. They are increasingly recognized as cancer drug targets. We analysed the binding of the patented Novartis inhibitor NVP-BHG712 (NVP) to EPHA2 and EPHB4. Unexpectedly, all tested commercially available NVP samples were regioisomers NVPiso with a single methyl group binding to an adjacent nitrogen atom compared to the patented compound. The two compounds of identical mass reveal different binding modes. Further, both, in vitro and in vivo experiments show that the isomers differ in their kinase affinity and selectivity.
HostingRepository	PRIDE
AnnounceDate	2018-09-05
AnnouncementXML	Submission_2018-09-05_05:50:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephanie Heinzlmeir
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-12 07:25:38	ID requested
⏵ 1	2018-09-05 05:50:15	announced

Tr, ö, ster A, Heinzlmeir S, Berger BT, Gande SL, Saxena K, Sreeramulu S, Linhard V, Nasiri AH, Bolte M, M, ü, ller S, Kuster B, M, é, dard G, Kudlinzki D, Schwalbe H, NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. ChemMedChem, 13(16):1629-1633(2018) [pubmed]

curator keyword: Biological

submitter keyword: Kinobeads, selectivity profiling, kinase inhibitor, EPH receptor

Bernhard Kuster
contact affiliation	Chair of Proteomics and Bioanalytics, Technische Universität München, Germany
contact email	kuster@tum.de
lab head
Stephanie Heinzlmeir
contact affiliation	Chair of Proteomics and Bioanalytics, Technische Universität München, Germany
contact email	stephanie.heinzlmeir@tum.de
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/2018/09/PXD009188

PRIDE project URI

• PRIDE
  1. PXD009188
     1. Label: PRIDE project
     2. Name: Single methyl group positioning opens new chemical space for EPH receptor kinase inhibition