Table 4.
Alphascreen IC50 values for displacement of H3K4me3-Bn from His-KDM7(PHD-JmjC) by AMI derivatives, and their inhibition of demethylation activity assessed by MALDI-TOF MS. Displacement – AlphaScreen displacement data. Catalytic – H3K9me2 demethylation assay using MALDI-TOF MS. NI: No inhibition seen at 100 μM. Average ± StdDev (n = 3 for AlphaScreen).
| Compounds | IC50 (µM) |
|||
|---|---|---|---|---|
| KDM7A (PHD-JmjC) (Displacement) |
KDM7A (PHD-JmjC) (Catalytic) |
KDM7B (PHD-JmjC) (Displacement) |
KDM7B (PHD-JmjC) (Catalytic) |
|
| AMI | 80 ± 26 | 83% (100 µM) | – | 22% (100 µM) |
| WAG-003 | NI | 17% (100 µM) | NI | 22% (100 µM) |
| WAG-005 | 16 ± 4 | 100% (100 µM) | NI | 33% (100 µM) |
| 1a | 295 ± 48 | 100% (100 µM) | NI | 95% (100 µM) |
| 2a | 149 ± 32 | 100% (100 µM) | 120 ± 32 | 89% (100 µM) |
| 2b | 5.6 ± 1.5 | 100% (100 µM) | 126 ± 34 | 32% (100 µM) |
| 2d | 88 ± 17 | 100% (100 µM) | >300 | 24% (100 µM) |