Inhibition of human 2OG oxygenases by N-hydroxythiazole analogues bearing different terminal sulfonamide substituents.
| Entry | Cmpda |
|
IC50 [μM]b | ||||
|---|---|---|---|---|---|---|---|
| R | FIHc | PHD2d | AspHe | KDM4Af | JMJD5g | ||
| i | 26 |
|
0.45 ± 0.17 | 12.4 ± 0.8 | 37.8 ± 11.3 | >100 | 12.5 ± 1.0 |
| ii | 33 |
|
0.39 ± 0.04 | 8.0 ± 0.2 | 30.3 ± 12.6 | >100 | 11.9 ± 1.8 |
| iii | 34 |
|
0.44 ± 0.03 | 14.6 ± 3.2 | 35.0 ± 0.0 | >100 | 18.5 ± 1.0 |
| iv | 35 |
|
0.46 ± 0.01 | 9.2 ± 0.4 | 28.8 ± 8.9 | >100 | 37.7 ± 0.9 |
| v | 36 |
|
0.46 ± 0.01 | 9.8 ± 0.5 | 36.6 ± 2.8 | >100 | 16.0 ± 6.8 |
| vi | 37 |
|
0.47 ± 0.07 | 15.2 ± 3.6 | 36.0 ± 0.7 | >100 | 63.2 ± 6.1 |
| vii | 38 |
|
0.26 ± 0.01 | 3.1 ± 0.1 | 30.2 ± 10.9 | >100 | 31.9 ± 2.0 |
| viii | 39 |
|
0.29 ± 0.03 | 3.1 ± 0.2 | 29.8 ± 4.3 | >100 | 8.6 ± 0.2 |
| ix | 40 |
|
0.45 ± 0.08 | 5.2 ± 1.1 | 40.1 ± 2.2 | >100 | 62.8 ± 0.4 |
| x | 41 |
|
0.47 ± 0.07 | 11.2 ± 2.3 | 30.3 ± 8.0 | >100 | 15.4 ± 7.1 |
| xi | 42 |
|
0.28 ± 0.02 | 6.9 ± 0.5 | 43.1 ± 18.7 | >100 | 7.2 ± 2.8 |
| xii | 43 |
|
0.81 ± 0.18 | 9.9 ± 0.5 | 35.5 ± 3.2 | >100 | 17.4 ± 6.0 |
a
All chiral N-hydroxythiazole derivatives were prepared as racemic mixtures.
b
Mean average ± SD of two independent experiments (each composed of technical duplicates).
c
Using 0.15 μM FIH, 10.0 μM 2OG and 5.0 μM HIF-1α C-TAD788–822.61
d
Using 0.15 μM PHD2181–426, 10.0 μM 2OG and 5.0 μM HIF-1α CODD556–574.61
e
Using 0.05 μM His6-AspH315–758, 3.0 μM 2OG and 1.0 μM hFX-CP101–119.58
f
Using 0.15 μM KDM4A, 10.0 μM 2OG and 10.0 μM H31–15K9me31–15.69
g
Using 0.15 μM JMJD5, 2.0 μM 2OG and 2.0 μM RSP6128–148.70 Inhibition assays were performed using SPE-MS as described in the ESI.