Journal Article

PUBDB-2019-00188

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family

Tröster, A. ; Heinzlmeir, S. ; Berger, B.-T. ; Gande, S. L. ; Saxena, K. ; Sreeramulu, S. ; Linhard, V.Extern* ; Nasiri, A. H. ; Bolte, M. ; Müller, S. ; Kuster, B. ; Médard, G. (Corresponding author) ; Kudlinzki, D. (Corresponding author)Extern* ; Schwalbe, H. (Corresponding author)Extern*

2018
Wiley-VCH Weinheim [u.a.]

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Please use a persistent id in citations: doi:10.1002/cmdc.201800398

Abstract: Erythropoietin‐producing hepatocellular (EPH) receptors are transmembrane receptor tyrosine kinases. Their extracellular domains bind specifically to ephrin A/B ligands, and this binding modulates intracellular kinase activity. EPHs are key players in bidirectional intercellular signaling, controlling cell morphology, adhesion, and migration. They are increasingly recognized as cancer drug targets. We analyzed the binding of NVP‐BHG712 (NVP) to EPHA2 and EPHB4. Unexpectedly, all tested commercially available NVP samples turned out to be a regioisomer (NVPiso) of the inhibitor, initially described in a Novartis patent application. They only differ by the localization of a single methyl group on either one of two adjacent nitrogen atoms. The two compounds of identical mass revealed different binding modes. Furthermore, both in vitro and in vivo experiments showed that the isomers differ in their kinase affinity and selectivity.

Note: (c) Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim;Post referee fulltext in progress; Embargo 12 months from publication

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Contributing Institute(s):

1. DOOR-User (DOOR)
2. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (POF3-622) (POF3-622)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; No Authors Fulltext ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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