Table 1 IC50 values for JMJD5FL inhibitors that likely bind in the 2OG cosubstrate pocket. A full-length JMJD5 construct (aa 1–416, JMJD5FL) was used in the inhibition assays. IC50 values were determined using MALDI-TOF-based hydroxylation assays with 10 µM JMJD5FL, 100 µM Fe(II), 400 µM ascorbate, 50 µM 2OG and 100 µM substrate RpS6129-144 (VPRRLGPKRASRIRKL) in the presence of varied concentrations of inhibitors (0–10 mM). Values represent mean (n = 3) ± SD.
IC50 (µM) | |
|---|---|
TCA cycle intermediates | |
Citrate5 | 820 ± 1.8 |
Fumarate5 | 1161 ± .1.4 |
d-2HG5 | 1268 ± 1.5 |
Isocitrate5 | 1294 ± 2 |
l-2HG5 | 340 ± 1.3 |
Malate5 | 1604 ± 1.4 |
Oxaloacetate5 | 85 ± 1.4 |
Pyruvate5 | 500 ± 1.6 |
Succinate5 | 840 ± 1.4 |
2OG mimetics | |
NOG5 | 6 ± 1.4 |
2.4-PDCA5 | 12 ± 1.4 |
2.4-BPDCA5 | 66 ± 1.5 |
45 | 53 ± 1.4 |
IOX138 | 96 ± 1.7 |
PHD2 inhibitors | |
GSK127886336 | 9 ± 1.2 |
FG459285 | 239 ± 1.9 |
Vadadustat86 | 54 ± 1.5 |
AKB-689987 | 288 ± 1.5 |
KDM inhibitors | |
GSK-J119 | 67 ± 1.5 |
KDM5-C4920 | 621 ± 1.4 |
ML-32437 | 15 ± 1.4 |