All of us are looking forward to see how this will perform in the daily field battles we must fight against ticks and fleas. “
“To date, no therapeutic compound administered per os has had the attributes required to effectively kill both fleas and ticks on dogs safely for a month or more ( Beugnet and Franc, 2012). Cythioate, an organophosphate, was the first BTK activity inhibition oral agent to kill fleas but the short duration of its efficacy (∼1 day; Gordon, 1995), variable efficacy against fleas ( Arther et al., 1989), and poor safety profile limited its use. Nitenpyram, a closely related analog of the neonicotinoid, imidacloprid,

has high levels of effectiveness against fleas only, and its half-life is such that its activity lasts but a single day ( Cadiergues et al., 1999). Spinosad www.selleckchem.com/products/epacadostat-incb024360.html was the first oral agent to provide month long activity with good effectiveness but primarily against fleas ( Snyder et al., 2007). Herein, we reveal the structure of afoxolaner, a novel member of an isoxazoline class of compounds, and describe the initial preclinical program in dogs against fleas and ticks using oral administration. Isoxazoline insecticide represents a new class of potent ectoparasiticides, including afoxolaner, but also fluralaner, amongst others (Ozoe et al., 2010, Garcia-Reynaga et al., 2013 and Gassel et al., 2014). The proof of concept studies presented here

were not conducted with a final formulation to be registered as a veterinary medicine. Initial in vitro studies revealed remarkable activity of afoxolaner against

fleas, and subsequent in vivo testing in dogs demonstrated outstanding effectiveness against fleas and ticks for an entire month following a single, low dose oral administration. Multi-month dosing tests further defined the effective oral dosage and safety of afoxolaner in dogs. Lastly, we outline the insecticidal/acaricidal mode of action of this compound and the class. The history of insecticidal isoxazolines already can be traced back to the discovery of the phthalic and the anthranilic diamides, and Lahm et al. (2013) have recently described the high levels of activity of a class of 4-azolylphenyl isoxazoline compounds for agricultural use. The isoxazoline compounds having both insecticidal and acaricidal activities have been proven to act on specific GABA/glutamate receptor inhibiting the chloride ion channels of arthropods (Ozoe et al., 2010, Garcia-Reynaga et al., 2013 and Gassel et al., 2014). The authors discovered a group of naphthalene isoxazoline compounds displaying remarkable activity against the cat flea (Ctenocephalides felis) and afoxolaner was selected as a representative compound for further testing and evaluation. The molecular structures of afoxolaner and of isoxazoline CPD1, a representative of the azolylphenyl isoxazoline class, are provided in Fig. 1.