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.

From: Structural analysis of the 2-oxoglutarate binding site of the circadian rhythm linked oxygenase JMJD5

 

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