Table 1.
Inhibitory potency of BPN14770 against human and mouse PDE4 subtypes and isoforms
| Species | Enzyme | Form | Mutationsa | BPN14770 IC50 (nM) | Rolipram IC50 (nM) |
|---|---|---|---|---|---|
| Human | PDE4D7 | Dimer | Native | 1018 ± 239 | 675 ± 8.5 |
| Human | PDE4D7 | Dimer | S129D(PKA), S654A(ERK), S656A(ERK) | 7.8 ± 1.8 | 32 ± 10 |
| Human | PDE4D3 | Dimer | S54D(PKA), S579A(ERK), S581A(ERK) | 7.4 ± 2 | 29 ± 11 |
| Human | PDE4D2 | Monomer | S413A(ERK), S415A(ERK) | 127 ± 1.2 | 142 ± 51 |
| Human | PDE4B1 | Dimer | S133D(PKA), S659A(ERK), S661A(ERK) | 2013 ± 256 | 175 ± 36 |
| Mouse | PDE4D7 | Dimer | S129D(PKA) | 133 ± 18 | 30 ± 17 |
| Mouse | PDE4D7 | Dimer | S129D(PKA), Y271F(UCR2) | 2.9 ± 0.3 | 36 ± 2.5 |
| Mouse | PDE4B3 | Dimer | S133D(PKA) | 2124 ± 527 | 223 ± 34 |
aPKA-activating mutation of serine to aspartic acid to mimic phosphorylation; ERK-null mutation of serine to alanine to prevent phosphorylation; UCR2 replacement of tyrosine by phenylalanine to humanize the mouse PDE4D UCR2