The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis

• DOI: 10.1007/s10456-010-9183-z
• Publication Date: 2010-08-28T03:28:14Z
• Authors: Georg Martiny-Baron; Philipp Holzer; Eric Billy; Christian Schnell; Joseph Brueggen; Mireille Ferretti; Niko Schmiedeberg; Jeanette M. Wood; Pascal Furet; Patricia Imbach
• Keywords: Angiogenesis inhibitor

EphB4 and its cognitive ligand ephrinB2 play an important role in embryonic vessel development vascular remodeling. In addition, several reports suggest that this receptor pair is also involved pathologic formation adults including tumor angiogenesis. Eph/ephrin signaling a complex phenomena characterized by forward through the tyrosine kinase of ephrin reverse various protein–protein interaction domains phosphorylation motifs ligands. Therefore, interfering with EphR/ephrin means targeted gene ablation, soluble receptors, dominant negative mutants or antisense molecules often does not allow to discriminate between inhibition signaling. We developed specific small molecular weight inhibitor kinase, NVP-BHG712, which inhibits activity low nanomolar range cellular assays showed high selectivity for targeting when profiled against other kinases biochemical as well cell based assays. Furthermore, NVP-BHG712 shows excellent pharmacokinetic properties potently autophosphorylation tissues after oral administration. vivo, VEGF driven formation, while it has only little effects on (VEGFR) vitro The data shown here close cross talk VEGFR EphR during formation. addition established function remodeling endothelial arterio-venous differentiation, appears be mediator induced angiogenesis since sufficient inhibit