Structure and activity of plasmin and other direct thrombolytic agents

Thrombosis Research
V Novokhatny

Abstract

The physiological or pharmacological dissolution of thrombi is ultimately accomplished by the serine protease plasmin. Plasmin is derived from its precursor plasminogen in a reaction catalyzed by plasminogen activators (PAs) such as tissue-type plasminogen activator (tPA). In the middle of the last century, plasmin was investigated as a potential thrombolytic agent. However, technical obstacles led to the abandonment of this agent, and by the 1970s PAs had become the standard of care for pharmacological management of various thrombotic conditions. Talecris Biotherapeutics has developed a methodology to prepare the plasmin product (Human) TAL-05-00018 that is rendered inactive by low pH (pH 3.0-4.0) until it is delivered directly to the neutral environment of a thrombus by catheter-assisted administration. TAL-05-00018 undergoes a rigorous manufacturing process to ensure a final product free from unactivated plasminogen, streptokinase, enveloped and non-enveloped viruses and prion proteins; generating an extremely high-purity product with a shelf life of three years at ambient temperature. TAL-05-00018 has shown promise in in vitro and pre-clinical studies, and in early clinical trials, demonstrating a dose-dependant reduction i...Continue Reading

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Citations

Mar 31, 2011·Toxicon : Official Journal of the International Society on Toxinology·Cho Yeow Koh, R Manjunatha Kini
Sep 25, 2010·Biomaterials·Kristen M LorentzJeffrey A Hubbell
Mar 25, 2014·Medicinal Research Reviews·Rami A Al-Horani, Umesh R Desai
Dec 1, 2009·Journal of Thrombosis and Haemostasis : JTH·V J Marder, V Novokhatny
Jan 31, 2015·PloS One·Manuel CorreiaMaria Teresa Neves-Petersen
Nov 16, 2017·Microbial Cell Factories·Yanying XuDeqiang Wang

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