title: Molecular modeling as a new approach to the development of urokinase inhibitors.
abstract: Proteolytic activity of urokinase plays an important role in negative remodeling of blood vessels, restenosis, tumor angiogenesis, and metastasizing, which necessitates the development of selective urokinase inhibitors. Using methods of computer modeling (docking, post processing, and direct docking) and quantum chemistry, we selected substances from the large compound database, analyzed their structures, and experimentally verified their inhibitor activity. New urokinase inhibitor candidates were proposed based on the theoretical predictions and experimental verification of compound activities. The process of modifying urokinase inhibitors based on (benzothiazol-3-yl)guanidine was developed. A new urokinase inhibitor (5-brom-benzothiazol-3-yl)guanidine, that can be effective for regulation of vascular remodeling and tumor angiogenesis, was created.
authors.affiliation: Russian Cardiology Research-and-Production Complex, Ministry of Health of the Russian Federation, Moscow, Russia.
authors.forename: I B
authors.initials: IB
authors.lastname: Beloglazova
authors.forename: O S
authors.initials: OS
authors.lastname: Plekhanova
authors.forename: E V
authors.initials: EV
authors.lastname: Katkova
authors.forename: K D
authors.initials: KD
authors.lastname: Rysenkova
authors.forename: D V
authors.initials: DV
authors.lastname: Stambol'skii
authors.forename: V B
authors.initials: VB
authors.lastname: Sulimov
authors.forename: V A
authors.initials: VA
authors.lastname: Tkachuk
mesh_terms: D001798:Blood Proteins / Q000737:chemistry*; D008958:Models, Molecular; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
chemical_list: D001798:Blood Proteins; C031220:urokinase inhibitor; D014568:Urokinase-Type Plasminogen Activator