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From Snake Venom's Disintegrins and C-Type Lectins to Anti-Platelet Drugs

期刊

TOXINS
卷 11, 期 5, 页码 -

出版社

MDPI
DOI: 10.3390/toxins11050303

关键词

snake venom; Tirofiban; Eptifibatide; Vipegitide; anti-platelet drug; acute coronary syndrome; percutaneous coronary intervention; clinical trial; adverse effect

资金

  1. German-Israeli Foundation [GIF-994-3.9/2008]
  2. National Cancer Institute [1R01CA133262-01A2, 1R01CA100145-01A1]

向作者/读者索取更多资源

Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of IIb3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of 21 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects.

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