Fig. 1.

Exemplar long-form PDE4 activator compound series. (A) An N-substituted-2-(3-aryl-1H-1,2,4-triazol-1-yl)acetamide chemotype was identified with long-form PDE4 activation properties, as exemplified here with 2-(3-(4-chloro-3-fluorophenyl)-5-ethyl-1H-1,2,4-triazol-1-yl)-N-(3,5-dichlorobenzyl)acetamide (MR-L2). (B) MR-L2 activates representative long-form PDE4 enzymes from each PDE4 family. Error bars represent SD of at least four independent experiments. (C) MR-L2 did not activate exemplar short isoforms of PDE4A, B, and D families (PDE4C expresses no short-form variants). (D) MR-L2 does not activate an engineered construct expressing a truncated core catalytic domain of PDE4D without UCR1, UCR2, and C-terminal tail. Data from n = 4 separate experiments shown as mean ± SD.