Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA)

H Matthews, M Ranson, JDA Tyndall…

Index: Matthews, Hayden; Ranson, Marie; Tyndall, Joel D.A.; Kelso, Michael J. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 22 p. 6760 - 6766

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Citation Number: 14

Abstract

A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, Ki= 7μM), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selective optimization of amiloride's structure for more potent ...