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. 2022 Mar 4;12(6):2905–2922. doi: 10.1016/j.apsb.2022.02.029

Table 4.

Kinase inhibitory activities of compounds 42–56 against PAK4.

Image 44
Compd. R3 PAK4 Ki (nmol/L)a PAK1 Ki (nmol/L)b A549c cLogPd PSAd LEf/LLEg
42 Image 45 6.6 4990 65%h 3.206 124.689 0.35/4.97
43 Image 46 42.6 1614 56% 3.208 124.751 0.29/4.16
44 Image 47 8.3 4237 39% 2.803 127.28 0.32/5.28
45 Image 48 25.6 2368 71% 2.791 117.883 0.30/4.80
46 Image 49 48.2 NDi 64% 3.093 115.319 0.29/4.22
47 Image 50 3.4 6986 57% 2.821 127.214 0.34/5.65
48 Image 51 5.6 7130 52% 2.828 125.297 0.33/5.42
49 Image 52 207.4 ND 54% 2.564 129.483 0.27/4.12
50 Image 53 27.2 ND ND 3.167 115.684 0.31/4.40
51 Image 54 25.5 6342 68% 3.174 115.624 0.31/4.42
52 Image 55 30.9 ND 63% 2.026 144.108 0.31/5.48
53 Image 56 22.7 2867 63% 3.176 124.552 0.31/4.47
54 Image 57 148.3 ND ND 3.301 123.455 0.27/3.53
55 Image 58 10.2 6025 32% 2.835 125.298 0.32/5.16
56 Image 59 18.1 4990 73% 2.575 129.268 0.31/5.17
GNE-2861 35.3 3135 62%g 3.41 103.298 0.34/4.04
a

PAK4 kinase inhibition was determined using a homogeneous time-resolved fluorescence (HTRF) assay. The Ki values are the average of two independent experiments reported as the mean value.

b

PAK1 kinase inhibition was determined using a FRET-based Z′-Lyte assay. The Ki values are the average of at least two duplicate experiments. SEM < ±20%.

c

Effect of compounds on the cell migration of A549 with the concentration of 5 μmol/L. Cell migration was determined by a wound-healing assay. Data are the results of at least two independent assays.

d

The clogP values and polar surface area were calculated by the Qikprop software.

f

Ligand efficiency = (−1.4 Log Ki)/(n heavy atoms).

g

Ligand lipophilicity efficiency = (−Log Ki) − (cLogP).

h

Effect of compounds on the cell mobility of A549 with a concentration of 20 μmol/L. Cell migration was determined by a wound-healing assay.

i

ND = not determined.