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1. Field of the Invention
The present invention relates to compounds that inhibit urokinase-type plasminogen activator receptor (uPAR). More specifically, the present invention relates to inhibitors of urokinase-type plasminogen activator receptor that are used in therapeutic compositions and methods of using such inhibitors for the treatment of pathological conditions.
2. Background Art
Urokinase-type plasminogen activator receptor (uPAR) is an integral membrane glycoprotein that is highly expressed in metastatic cancer cells and is expressed in the human body at low levels in adult tissues and fetal tissues. uPAR binds to urokinase plasminogen activator (uPA) via its N-terminal segment and uPA converts plasminogen to plasmin. uPA is a serine protease that acts on extracellular matrix (ECM) proteins and stimulates the breakdown of proteins such as collagen, fibronectin and laminin via activation of plasminogen. uPAR is a disulfide-linked homodimer and two uPAR monomers in a heterodimer are linked by a disulfide bond. uPAR is secreted as a glycosylphosphatidylinositol (GPI)-anchored receptor. When a cell is attached to a substrate or a matrix, uPAR binds to uPA via the uPA binding domain, which is located in the N-terminal segment of uPAR. The binding of uPA to uPAR stabilizes the binding of uPA to vitronectin, resulting in increased proteolytic activation of plasminogen to plasmin. The uPA binding domain also binds https://thenationalcolleges.org/?p=2626
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