title: Molecular and pharmacodynamic characteristics of the novel multi-target tumor growth inhibitor ZK 304709.
abstract: Loss of cell cycle control and tumor-induced neovascularization are major drivers of human tumor growth. The multi-target tumor growth inhibitor ZK 304709 is a nanomolar inhibitor of cyclin-dependent kinases 1, 2, 4, 7 and 9, as well as vascular endothelial growth factor receptor tyrosine kinase 1-3 and of platelet-derived growth factor receptor beta tyrosine kinase. The multi-targeted mode of action of ZK 304709 acting on cell cycle and angiogenesis resulted in superior efficacy compared to standard chemotherapeutic compounds both in s.c. human tumor xenografts as well as orthotopic human pancreatic carcinoma models.
authors.affiliation: Schering AG/BerlexLaboratories INC, Corporate Research Oncology Muellerstrasse 178, 13353, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Siemeister
authors.forename: U
authors.initials: U
authors.lastname: Luecking
authors.forename: C
authors.initials: C
authors.lastname: Wagner
authors.forename: K
authors.initials: K
authors.lastname: Detjen
authors.forename: C
authors.initials: C
authors.lastname: Mc Coy
authors.forename: Klaus
authors.initials: K
authors.lastname: Bosslet
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C000622581:ZK 304709; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D017346:Protein Serine-Threonine Kinases