title: Inhibition of VEGF mediated post receptor signalling pathways by recently developed tyrosine kinase inhibitor in comparison with sunitinib.
abstract: Inhibition of angiogenesis involves blocking of tyrosine kinases (TK) implicated in signalling of vascular endothelial growth factor receptors (VEFGR). The inhibition of TK results in a disruption of Ras/Raf/MEK/ERK1/2 and PI3K/Akt signalling pathways. We evaluated recently developed TK inhibitor 22SYM and compared its anti-angiogenic effects with an approved multitargeted TK inhibitor sunitinib L-malate (sunitinib). Both compounds significantly inhibited migration and proliferation of human umbilical vein endothelial cells and ERK1/2 and Akt phosphorylation induced by VEGF. The lower inhibitory activity of 22SYM probably reflects its lower bioavailability and higher specific binding to VEGFR2 TK, which may decrease its potential side effects and toxicity in comparison with sunitinib.
authors.affiliation: Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovak Republic. moravcikr@fns.uniba.sk.
authors.forename: Roman
authors.initials: R
authors.lastname: Moravčík
authors.forename: Katarína
authors.initials: K
authors.lastname: Stebelová
authors.forename: Andrej
authors.initials: A
authors.lastname: Boháč
authors.forename: Michal
authors.initials: M
authors.lastname: Zeman
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000008:administration & dosage*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib