Warfarin Promoter for Enhanced Rodenticide Efficiency
WiSys is currently seeking a strategic partner to assist in such further development providing a route to market for the commercialization of lead analogues.
Patent Number: 8,765,982
Patent Issued Date: July 1, 2014 (PDF)
Stage of Development:
The lead compound, UWEC-K2 can be readily synthesized along with its simple metabolites and can be provided to partners for further development and testing.
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