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Phosphomannopentaose sulfate (PI-88): heparan sulfate mimetic with clinical potential in multiple vascular pathologies Khachigian LM; Parish CRCardiovasc Drug Rev 2004[Spr]; 22 (1): 1-6The sulfated oligosaccharide PI-88 is a potent antiangiogenic, antitumor and anti-metastatic agent derived from yeast. It is primarily composed of sulfated phosphomannopentaose and phosphomannotetraose oligosaccharide units and is presently under evaluation in Phase II clinical trials for anticancer efficacy. PI-88 inhibits the heparan sulfate-degrading enzyme heparanase, exhibits antiangiogenic activity and has anticoagulant properties mediated by heparin cofactor II. It also inhibits vascular smooth muscle cell proliferation, kinase signalling and arterial intimal thickening following balloon injury. Many heparan sulfate-binding growth factors require heparan sulfate as a co-receptor in order to effectively deliver growth signals to cells. Thus, the antiangiogenic and antirestenotic activity of PI-88 may be at least partially due to this highly sulfated oligosaccharide competing with the interaction of growth factors, such as FGF-2 and VEGF, with cell surface heparan sulfate. This heparan sulfate mimetic has, therefore, multiple functions and therapeutic potential in a variety of vascular disorders.|Angiogenesis Inhibitors/chemistry/pharmacology[MESH]|Anticoagulants/chemistry/pharmacology[MESH]|Antineoplastic Agents/chemistry/*pharmacology[MESH]|Coronary Restenosis/prevention & control[MESH]|Heparitin Sulfate/*chemistry[MESH]|Humans[MESH]|Molecular Mimicry[MESH]|Oligosaccharides/chemistry/*pharmacology[MESH] |
