UR-3216: A New Generation Oral Platelet GPIIb / IIIa Antagonist

Author(s): Yasuhiro Aga, Kosuke Baba, Susan Tam, Takayuki Nakanishi, Kenji Yoneda, Jun-ichiro Kita, Hitoshi Ueno.

Journal Name: Current Pharmaceutical Design

Volume 10 , Issue 14 , 2004


Various oral platelet GPIIb / IIIa receptor antagonists have undergone clinical investigations, but to date without success. Various factors have been proposed to explain their failure such as low affinity for the receptor, large peak / trough ratio, low bioavailability, partial agonist activity and pro-aggregatory effect. Efforts to discover a truly effective, safe, oral antagonist led to the discovery of UR-3216 (Fig. 1). The active form of UR-3216, UR-2922, possessed a high affinity for the human platelet receptor (Kd < 1 nM) with a slow dissociation rate (koff = 90 min) in vitro. UR-2922 induced no ligandinduced binding sites (LIBS) expression or prothrombotic activity in human platelets, distinctly different from orbofiban and other small molecule antagonists. To date, UR-2922 is the only high affinity GPIIb / IIIa antagonist without LIBS expression. In vivo characteristics of UR-3216 showed prolonged duration of efficacy ( > 24 h) with its favorable pharmacokinetic profile, superior to all the other oral GPIIb / IIIa antagonists. UR-3216 showed high bioavailability, rapid bioconversion to the active form and biliary excretion. UR-3216 is a novel, orally active GPIIb / IIIa antagonist of a new generation, which has substantially improved the crucial compounding factors and will be useful for the treatment of cardiovascular diseases.

Keywords: ur-3216, antiplatelet drug, thrombosis

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Article Details

Year: 2004
Page: [1597 - 1601]
Pages: 5
DOI: 10.2174/1381612043384592
Price: $58

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