Efficacy of PDE11A inhibitors in a cell model of aging-like PDE11A4
protein abnormalities. (A) 1, (B) 14b, and
(C) 23b all reduce PDE11A4 cAMP hydrolytic activity,
but 23b appears more potent as it was the only compound
with robust inhibition noted at 1 μM (note that 1 and 23b were simultaneously cultured and processed).
The same pattern was observed for the ability of (D) 1, (E) 14b, and (F) 23b to inhibit PDE11A4
cGMP hydrolytic activity, again with 23b exhibiting greater
potency. Comparison of 100 μM dose groups across compounds suggests
that 14b and 23b are both more efficacious
than 1, with both showing stronger inhibition of PDE11A4
cAMP and cGMP hydrolytic activity. *vs DMSO + PDE11A4 within experiment, P < 0.05–0.001; #vs 1 at the same
concentration, P < 0.05–0.001. Data graphed
mean ± SEM.