Table II.
Compounds | Cytochrome P450 isozyme inhibition (IC 50 in μM) a | ||||||
---|---|---|---|---|---|---|---|
1A2 | 2C19 | 2C9 | 2D6 | 3A4 (M) | 3A4 (T) | ||
1 | >200bc | >200bc | >200bc | >200bc | >200bc | >200bc | |
2 | >200bc | >200bc | >200bc | >200bc | >200bc | >200bc | |
3 | >200bc | >200bc | >200bc | >200b | >200b | >200b | |
4 | >200b | >200bc | >200bc | >200bc | >200b | >200b | |
5 | >200bc | >200bc | >200bc | >200b | 111.89 (17.8) | 98.82 (11.6) | |
6 | >200bc | >200bc | >200bc | >200bc | 48.83 (5.6) | 59.90 (2.8) | |
7 | >200b | >200bc | >200bc | >200b | >200b | >200b | |
8 | 10.93 (4.1) | >200b | 37.96 (3.3) | 50.84 (21.2) | >200bc | 123.12 (31.8) | |
9 | 2.68 (0.5) | 59.15 (11.6) | 22.93 (2.3) | 5.43 (2.0) | 151.15 (88.2) | 43.04 (10.2) | |
10 | >200b | >200b | >200b | >200b | >200b | >200b | |
11 | 86.59 (9.6) | 50.54 (3.3) | 42.76 (5.2) | 59.34 (7.1) | 154.35 (75.9) | 131.61 (33.1) | |
12 | 22.21 (6.6) | 9.76 (3.4) | 2.46 (0.8) | 4.19 (1.7) | 15.95 (6.2) | 34.36 (13.8) | |
13 | 27.72 (11.6) | 49.95 (10.6) | 31.56 (7.2) | 191.44 (57.4) | 51.29 (16.6) | 55.54 (8.5) | |
14 | 12.92 (4.7) | 24.16 (9.6) | 7.10 (0.7) | 52.00 (32.5) | >200b | >200b | |
15 | >200b | >200bc | >200bc | >200bc | >200bc | >200bc | |
16 | >200b | >200bc | >200bc | >200bc | >200bc | >200bc | |
17 | 1.44 (0.3) | 50.75 (9.5) | 28.84 (3.1) | 33.86 (1.4) | >200b | >200b | |
18 | 21.80 (4.1) | 39.15 (9.2) | 8.46 (5.2) | 4.61 (2.6) | 57.88 (27.3) | 22.33 (9.6) | |
19 | >200b | >200bc | >200bc | >200b | >200bc | >200bc | |
20 | 49.80 (17.0) | 13.55 (1.8) | 17.63 (6.7) | >200b | 10.96 (4.3) | 14.51 (2.5) | |
21 | 1.14 (0.1) | 15.02 (1.1) | 6.42 (0.8) | 5.94 (0.7) | 76.13 (10.5) | 22.88 (5.9) | |
22 | 18.33 (2.9) | 105.90 (20.1) | 30.76 (4.0) | 18.27 (3.5) | >200b | >200b | |
23 | 1.99 (0.5) | 6.77 (1.5) | 0.70 (0.2) | 10.27 (5.0) | 90.66 (8.5) | 41.13 (9.8) | |
24 | 2.83 (1.4) | 22.78 (7.0) | 19.22 (7.8) | 3.86 (1.3) | 12.32 (7.6) | 38.44 (3.7) | |
25 | 1.45 (0.1) | 59.02 (14.2) | 8.24 (1.4) | >200b | >200b | >200b | |
26 | 5.33 (0.7) | 19.46 (3.8) | 2.52 (0.9) | 6.18 (4.1) | 21.31 (11.1) | 31.79 (8.1) | |
27 | 8.38 (2.5) | 8.58 (2.4) | 19.41 (1.5) | 20.19 (3.5) | 23.48 (1.3) | 52.58 (12.9) | |
28 | 0.72 (0.4) | 12.14 (3.3) | 7.18 (2.8) | 1.75 (0.1) | 12.58 (1.1) | 29.95 (7.3) | |
29 | 8.11 (1.8) | 66.48 (11.3) | 16.03 (2.8) | 22.10 (4.2) | >200b | >200b | |
30 | 1.34 (0.4) | 31.75 (2.6) | 0.40 (0.2) | 26.46 (1.8) | >200b | 79.25 (4.9) | |
31 | 0.48 (0.1) | 5.91 (1.6) | 0.90 (0.1) | 3.15 (0.1) | 7.99 (1.3) | 41.36 (10.2) | |
32 | 1.99 (0.6) | 12.50 (0.3) | 18.97 (0.4) | 3.39 (1.0) | 6.00 (1.3) | 49.36 (7.0) | |
33 | 2.16 (0.2) | 2.89 (0.3) | 8.83 (2.2) | 3.26 (0.3) | 9.20 (1.0) | >200b | |
34 | 4.51 (1.3) | 3.91 (1.1) | 0.65 (0.1) | 15.02 (6.9) | 20.57 (4.3) | 26.14 (1.8) | |
35 | 33.56 (6.5) | 18.20 (5.1) | 38.69 (11.3) | 98.79 (24.2) | 26.59 (2.2) | 44.62 (11.9) | |
36 | 3.12 (0.9) | 17.68 (10.8) | 4.52 (2.7) | 1.34 (0.4) | 7.97 (1.6) | 30.69 (0.5) | |
37 | 57.87 (3.8) | 59.01 (8.7) | 42.12 (17.9) | 19.32 (11.7) | 142.26 (43.4) | 78.24 (36.2) | |
38 | 1.19 (0.1) | 29.10 (4.4) | 0.12 (0.08) | 29.61 (10.2) | >200b | >200b | |
39 | 9.44 (1.6) | 16.35 (6.3) | 22.03 (2.0) | 6.49 (1.3) | 44.49 (21.7) | 26.72 (7.4) | |
40 | 40.96 (5.5) | 71.89 (16.5) | 27.71 (12.3) | 43.53 (25.9) | 25.83 (11.0) | 34.48 (4.9) |
Potent inhibitors (IC50 > 5 μM for 1A2, 2C9, 2C19, 2D6, and IC50 > 15 μM for 3A4) were italicized. Data in the brackets suggested standard error
3A4 (M) midazolam, 3A4 (T) testosterone
aStandard deviation of IC50 were presented in brackets. Values were obtained from triplicate tests
bIC50 >200 μM was agreed by triplicate tests
cWeak activation was observed