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. Author manuscript; available in PMC: 2020 Aug 24.
Published in final edited form as: J Med Chem. 2019 Apr 23;62(10):4884–4901. doi: 10.1021/acs.jmedchem.9b00193

Table 5.

PDE4 inhibitory activity of 28 and 29 compared to apremilast (30).

graphic file with name nihms-1617532-t0014.jpg
Compound Parameter PDE4D7-
S129D
dimer
activated		 PDE4D7-
S129(wt)
dimer basal		 PDE4B1-
S133D
dimer
activated		 PDE4D3-
S54D
dimer
activated		 PDE4D2
monomer		 PDE4D-cat
monomer
28 IC50 nM 7.8 ± 1.8 1018 ± 239 2013 ± 256 7.4 ± 2.0 127 ± 1.2 6561 ± 10
Hill Slope 0.55± 0.12 0.58 ± 0.11 0.92 ± 0.21 0.68 ± 0.14 0.60± 0.16 1.2 ± 0.10
 Imax%c 90.2 ± 4.8a * * 89 ±2.3 b * *
Count 15 9 6 5 4 3
29 IC50 nM d 0.8 ± 1.6 885 ± 2.2 128 ± 1.3 - - -
Hill Slope d 0.66± 0.03 0.50 ± 0.1 0.37 ± 0.04 - - -
Imax%c, d 88 ± 3.6 * * - -
Countd 2 2 2 - - -
30 (apremilast) IC50 nM 26 ± 1.3 32 ± 1.6 24 ± 1.2 23 ± 1.2 35 ± 1.3 21 ± 1.2
Hill Slope 1.0 ± 0.14 1.2 ± 0.3 1.0 ± 0.05 1.1 ± 0.14 1.1 ± 0.09 1.1 ± 0.11
Imax % 97 ± 3.5 96 ± 2.4 100 ± 0 98 ± 2.0 99 ± 1.0 98 ± 1.8
Count 8 6 2 5 4 3
a

Two-Way ANOVA (F(1.29) = 27.3, p <0.001; Sidak’s multiple comparisons test p= 0.0012

b

Two-Way ANOVA (F(1,29) = 27.3, p < 0.001; Sidak’s multiple comparisons test, p= 0.0019

c *

Imax could not be calculated due to incomplete inhibition curve

d

- not tested. Values tabulated are mean ± SD and Count -the number of times that the compound was tested.