Table 3.
The inhibition of human AspH, PHD2, FIH, and KDM4E by selected C‐3 functionalised 2,4‐PDCA derivatives.
|
Inhibitor |
IC50 AspH [μM][a,b] |
IC50 PHD2 [μM][a,c] |
IC50 FIH [μM][a,d] |
IC50 KDM4E [μM][a,e] |
|---|---|---|---|---|
|
1 |
0.03 ±0.01 |
5.29±3.35 |
5.03±2.06 |
0.18±0.0139 |
|
17 |
4.67 ±0.29 |
2.60 ±1.20 |
6.59 ±0.05 |
0.43 ±0.05 |
|
18 |
0.58 ±0.06 |
>50 |
43.0 ±3.9 |
2.45 ±0.59 |
|
25 |
3.95 ±0.33 |
>50 |
>50 |
2.36±0.13 |
|
26 |
7.66 ±1.45 |
>50 |
>50 |
5.71±0.04 |
|
29 |
0.28 ±0.11 |
>50 |
14.9 ±1.5 |
0.99 ±0.31 |
|
30 |
1.22 ±0.26 |
>50 |
46.1 ±3.2 |
3.69 ±0.85 |
|
31 |
1.86 ±1.06 |
>50 |
>50 |
3.57 ±0.38 |
|
32 |
3.67 ±0.74 |
>50 |
26.1 ±3.9 |
4.14±0.28 |
[a] Mean of two independent runs (n=2; mean ± SD). [b] Using 50 nM His6‐AspH315‐758 and 1.0 μM hFX‐CP101‐119 (Figure 2D). [c] Using 150 nM PHD2 and 5.0 μM C‐terminal oxygen‐dependent degradation domain fragment (HIF‐1α CODD, amino acids 558–574). [d] Using 150 nM FIH and 5.0 μM C‐terminal transactivation domain fragment (HIF‐1α CAD, amino acids 788–822). [e] Using 150 nM KDM4E and 10.0 μM of a variant of histone 3 (H31‐15K9me3, amino acids 1–15; Experimental Section)40. Enzyme inhibition assays were performed as described in the Experimental Section.