LX0702, a novel snake venom peptide derivative, inhibits thrombus formation via affecting the binding of fibrinogen with GPIIb/IIIa
LX0702, a novel snake venom peptide derivative, inhibits thrombus formation via affecting the binding of fibrinogen with GPIIb/IIIa
复制标题
LX0702是一种新型蛇毒肽衍生物，通过影响纤维蛋白原与GPIIb/IIIa的结合抑制血栓形成
DOI：
10.1016/j.jphs.2015.03.010
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发表时间：
2015-04-01
影响因子：
3.5
通讯作者：
Li, Zhiyu
中科院分区：
文献类型：
--
作者：
Kong, Yi;Wang, Ying;Li, Zhiyu
Based on the structure of AAP, a novel anti-thrombotic peptide from snake venom which we discovered in our previous study, more than 60 compounds were designed and synthesized. One of these termed as LX0702 exhibited stronger anti-platelet aggregation activity than AAP. This study aims to investigate the effects of LX0702 on anti-thrombotic formation and its underlying mechanism. We found that LX0702 inhibited platelet aggregation induced by ADP, thrombin and collagen in a dose dependent manner, with IC50 values of 49.90 +/- 2.03, 50.65 +/- 0.34 and 83.90 +/- 2.06 mu M, respectively. It also inhibited thrombus formation in the rat arterio-venous shunt model. In addition, the effect of LX0702 on hemostasis system was tested. Compared to control saline, bleeding time was not prolonged. Furthermore, the ELISA revealed that LX0702 inhibited fibrinogen binding with GPIIb/IIIa in a dose dependent manner with an IC50 value of 1.26 +/- 0.13 mu M. These findings clearly demonstrate that LX0702 has anti-platelet/antithrombotic effects without increased bleeding risk. Therefore it might be developed into an effective drug for the prevention or treatment of thrombotic diseases. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
