Pyriproxyfen is photostable and is available in a variety of formulations that permit persistence in the coats of treated dogs and cats. An analytical study of pyriproxyfen administered orally to cats at doses up to 50 mg/kg was unable to detect any drug in samples of hair. However, dogs and cats treated topically on the dorsal midline of the neck with and mg/kg as a 1% solution of pyriproxyfen had sustained levels of pyriproxyfen in their hair at concentrations above mg/kg for more than 48 d. Not unexpectedly, there was a clear concentration gradient from the site of application to the hair of the hindquarters and considerable interanimal variation in hair concentration. The minimum concentration causing inhibition of development of flea eggs has been shown to be mg/kg in hair.
The 19S regulatory particle is responsible for stimulating the 20S to degrade proteins. A primary function of the 19S regulatory ATPases is to open the gate in the 20S that blocks the entry of substrates into the degradation chamber.  The mechanism by which the proteasomal ATPase open this gate has been recently elucidated.  20S gate opening, and thus substrate degradation, requires the C-termini of the proteasomal ATPases, which contains a specific motif (., HbYX motif). The ATPases C-termini bind into pockets in the top of the 20S, and tether the ATPase complex to the 20S proteolytic complex, thus joining the substrate unfolding equipment with the 20S degradation machinery. Binding of these C-termini into these 20S pockets by themselves stimulates opening of the gate in the 20S in much the same way that a "key-in-a-lock" opens a door.  The precise mechanism by which this "key-in-a-lock" mechanism functions has been structurally elucidated.