Desmoteplase: discovery, insights and opportunities for ischaemic stroke

Abstract

Nature has provided a vast array of bioactive compounds that have been exploited for either diagnostic or therapeutic use. The field of thrombosis and haemostasis in particular has enjoyed much benefit from compounds derived from nature, notably from snakes and blood-feeding animals. Indeed, the likelihood that blood-feeding animals would harbour reagents with relevant pharmacology and with potential pharmaceutical benefit in haemostasis was not too far-fetched. Blood-feeding animals including leeches and ticks have evolved a means to keep blood from clotting or to at least maintain the liquid state, and some of these have been the subject of clinical development. A more recent example of this has been the saliva of the common vampire bat Desmodus rotundus, which has proven to harbour a veritable treasure trove of novel regulatory molecules. Among the bioactive compounds present is a fibrinolytic compound that was shown over 40 years ago to be a potent plasminogen activator. Studies of this vampire bat-derived plasminogen activator, more recently referred to as desmoteplase, revealed that this protease shared a number of structural and functional similarities to the human fibrinolytic protease, tissue-type plasminogen activator (t-PA) yet harboured critically important differences that have rendered this molecule attractive for clinical development for patients with ischaemic stroke.