Medicine and Health Sciences Commons^™

Small Molecule Antagonists Of The Urokinase (Upa): Urokinase Receptor (Upar) Interaction With High Reported Potencies Show Only Weak Effects In Cell-Based Competition Assays Employing The Native Upar Ligand, Melissa De Souza, Hayden Matthews, Jodi A. Lee, Marie Ranson, Michael J. Kelso

Illawarra Health and Medical Research Institute

Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA:uPAR interaction represent promising anti-tumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC50 1 = 0.8 nM, IC50 2 = 33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before …