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Lazarovici P , Marcinkiewicz C , Lelkes PI
From Snake Venom's Disintegrins and C-Type Lectins to Anti-Platelet Drugs
Toxins (Basel). 2019 May 27;11(5)
PMID: 31137917 PMCID: PMC6563238
AbstractSnake 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 alphaIIbbeta3 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 alpha2beta1 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.
Notes2072-6651 Lazarovici, Philip Marcinkiewicz, Cezary Lelkes, Peter I R01 CA133262/CA/NCI NIH HHS/United States R01 CA100145/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Switzerland Toxins (Basel). 2019 May 27;11(5). pii: toxins11050303. doi: 10.3390/toxins11050303.