WiSys Technologies

OVERVIEW

Warfarin is a “first-generation” anticoagulant that has been widely used as a multiple feeding rodenticide for more than 60 years. The prolonged use of warfarin as a rodenticide has, according to some accounts, led to the evolution of warfarin-resistant rodents. More powerful “second-generation” anticoagulant rodenticides were developed and introduced to combat resistance and kill rodents with a single feeding, but there are environmental concerns due to inadvertent poisoning larger predatory animals that ingest poisoned rodents. Recent EPA restrictions on rodenticides using second-generation anticoagulants have created a need for more potent first generation anticoagulants, i.e. warfarin. There is a great need specifically for new compounds that can be paired with first generation poisons to give enhanced rodenticide qualities that can kill rodents in a single feeding.

RESEARCH AND DEVELOPMENT

Earlier studies in a rodent model assessed the effects of lead compounds (UWEC-K1 and UWEC-K2) for their effects on blood clotting in the presence and absence of warfarin after 4 and 10 days of separate administration and co-administration of warfarin.  At day 4, UWEC-K2 demonstrated antagonistic effects with regard to warfarin activity, however at day 10, the compound was observed to act as a warfarin promoter enhancing the effect of warfarin to a significant degree.  Briefly, the prothrombin clotting time was increased almost an order of magnitude compared to the control and by a factor of over 4 relative to warfarin alone.  In addition, Factor VII levels were reduced by a factor of close to 20 compared to the control and by a factor of 3 relative to warfarin alone.  These preliminary data suggested that at 10 days, the UWEC-K2 molecule quadrupled the anticoagulant effect of warfarin.  Recent studies have been focused on elucidating UWEC-K2’s mechanism of action, and resulting new models propose an interaction among warfarin, UWEC-K2, and a native enzyme that modulates warfarin activity in vivo. Further in vitro and in vivo studies are required to validate this proposed model.  

Applications and Key Benefits

• As a synergistic rodenticide with warfarin
• Increases warfarin anticoagulant activity by up to 4x
• Non-toxic when administered without warfarin
• Likely not classified as a pesticide by the EPA
• As a synergistic rodenticide with analogues of warfarin
• Neither warfarin analogue nor the UWEC-K2 derivative is toxic alone