Affinities of crisaborole, compd2, compd3, compd4, apremilast, and roflumilast for PDE4 isoforms
| Compound | IC50 Value (No. of Independent Experiments) | |||||
|---|---|---|---|---|---|---|
| PDE4B2_cat | PDE4A1A | PDE4B1 | PDE4B2 | PDE4C1 | PDE4D7 | |
| nM | ||||||
| Crisaborole | 75 (2) | 55 (5) | 61 (5) | NT | 340 (4) | 170 (5) |
| Compd2 | 1.8 (2) | 6.4 (2) | 6.8 (2) | 4.4 (2) | 71 (2) | 12 (2) |
| Compd3 | 3.0 (2) | 6.5 (2) | 3.1 (2) | 2.1 (2) | 8.4 (2) | 4.6 (2) |
| Compd4 | 0.32 (10) | 2.3 (2) | 0.15 (2) | 0.22 (2) | 4.4 (2) | 0.36 (2) |
| Apremilast | 39 (1) | 8.9 (5) | 16 (4) | 23 (2) | 48 (4) | 12 (5) |
| Roflumilast | 0.47 (6) | 0.33 (2) | 0.28 (2) | 15 (2) | 0.95 (2) | 0.53 (2) |
PDE4B2_cat is the catalytic domain of human PDE4B2; the sequences of the catalytic domain of PDE4B1 and PDE4B2 are identical. The others are full-length human PDE4 enzymes. In the assays, 1.5 μM [3H]-cAMP was used as a substrate. NT, not tested.