Comparative Studies of a Humanized Anti-glycoprotein IIb/IIIa Monoclonal Antibody, YM337, and Abciximab on in Vitro Antiplatelet Effect and Binding Properties

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概要

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• The effects of YM337, the Fab fragment of a humanized anti-glycoprotein IIb/IIIa (GPIIb/IIIa) monoclonal antibody C4G1, on in vitro platelet function and binding properties were compared with those of abciximab, the Fab fragment of the human/murine chimeric anti-GPIIb/IIIa monoclonal antibody 7E3. Both agents completely inhibited platelet aggregation caused by all agonists tested except ristocetin. Further, both inhibited human platelet adhesion to von Willebrand factor, fibrinogen, fibronectin and subendothelial matrix with similar potency. Fibrinogen binding to washed platelets was dose-dependently inhibited by both agents. In binding assay using ^<125>I-YM337 and ^<125>I-abciximab, K_d values determined with platelet-rich plasma were 6.74±0.56 nM for YM337 and 6.65±1.45 nM for abciximab, and the number of binding sites were 42700±3000 for YM337 and 76000±5400 for abciximab. GPIIb/IIIa was precipitated from the solubilized fraction of platelets by both agents. In contrast, integrin α_Vβ_3 was precipitated from the solubilized fraction of human umbilical vein endothelial cells by abciximab but not by YM337. Fibrinogen binding to purified GPIIb/IIIa was dose-dependently inhibited by both agents. In contrast, vitronectin binding to purified integrin α_Vβ_3 was dose-dependently inhibited by abciximab but not by YM337, supporting the idea that abciximab reacts to integrin α_Vβ_3. Therefore, YM337 was suggested to bind to a different epitope of GPIIb/IIIa from abciximab. These results suggest that YM337 specifically acts on platelet GPIIb/IIIa receptors and has similar inhibitory properties on platelet aggregation and platelet adhesion to abciximab.

• 公益社団法人日本薬学会の論文
• 2002-08-01

著者

• SUZUKI Ken-ichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• KAWASAKI TOMIHISA

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• Kamohara Masazumi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Company, Ltd.

• SATO Kazuo

  Institute of Quantum Science, Nihon University

• Sato K

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• KAKU Seiji

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• YANO Shinya

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• IIZUMI Yuichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• Yano S

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Iizumi Y

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Kamohara Masazumi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Kawasaki Tomihisa

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Kawasaki Tomihisa

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical

• Yano Shinya

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Suzuki Ken-ichi

  Microbiology Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Suzuki Ken-ichi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Sato Kazuo

  Institule For Agricultural Research Tohoku University

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