Table 1.
Studies on 4‐hydroxypyrimidine containing inhibitors. Compounds were screened against PHD2181‐426 using HIF‐1α CODD and NODD substrates, FIH using HIF‐1α CAD peptide D788–L822, KDM4A using H3(1–15) K9Me3. PHD2, FIH, and KDM4A assays employed a RapidFire MS machine. Standard errors of the mean are reported (n=3).
|
| |||||
|---|---|---|---|---|---|
|
|
R |
PHD2 with HIF‐1α CODD IC50 μM |
PHD2 with HIF‐1α NODD IC50 μM |
FIH IC50 μM |
KDM4A IC50 μM |
|
6 |
precursor |
>25 |
>25 |
>25 |
>25 |
|
8 |
|
0.256±0.088 |
0.094±0.042 |
>25 |
>25 |
|
9 |
|
0.210±0.051 |
0.093±0.033 |
>25 |
20 |
|
10 |
|
0.396±0.180 |
0.122±0.065 |
>25 |
>25 |
|
11 |
|
0.950±0.185 |
0.359±0.110 |
>25 |
17 |
|
12 |
|
>25 |
>25 |
>25 |
>25 |
|
13 |
|
0.153±0.042 |
0.066±0.026 |
>25 |
>25 |
|
14 |
|
0.261±0.037 |
0.274±0.034 |
>25 |
23 |
|
15 |
|
0.213±0.064 |
0.101±0.023 |
>25 |
>25 |
|
16 |
|
0.093±0.039 |
0.027±0.012 |
>25 |
>25 |
|
17 |
|
13.275±3.4 |
3.95±1.62 |
>25 |
21 |
|
| |||||
|
18 |
|
0.253±0.047 |
0.127±0.056 |
>25 |
4.69 |
