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. 2023 Oct 27;14(43):12098–12120. doi: 10.1039/d3sc04253g

Inhibition of human 2OG oxygenases by N-hydroxythiazole analogues bearing carbocyclic linkers.

Entry Cmpda graphic file with name d3sc04253g-u24.jpg IC50 [μM]b
R FIHc AspHd PHD2e KDM4Af JMJD5g
i 20 graphic file with name d3sc04253g-u25.jpg 1.0 ± 0.0 23.3 ± 10.1 6.5 ± 1.8 >100 13.4 ± 6.5
ii 24 graphic file with name d3sc04253g-u26.jpg 0.45 ± 0.17 60.9 ± 24.1 5.2 ± 0.7 >100 29.1 ± 4.4
iii 25 graphic file with name d3sc04253g-u27.jpg 1.2 ± 0.2 >100 33.5 ± 1.0 >100 32.6 ± 6.7
iv 26 graphic file with name d3sc04253g-u28.jpg 0.50 ± 0.02 37.8 ± 11.3 12.4 ± 0.8 >100 12.5 ± 1.0
v 27 graphic file with name d3sc04253g-u29.jpg 0.87 ± 0.04 49.1 ± 1.7 11.0 ± 1.6 >100 13.4 ± 1.0
vi 28 graphic file with name d3sc04253g-u30.jpg 2.1 ± 1.5 24.9 ± 12.0 12.7 ± 1.8 >100 2.6 ± 0.2
vii 29 graphic file with name d3sc04253g-u31.jpg >100 >100 >100 >100 >100
viii 30 graphic file with name d3sc04253g-u32.jpg 1.7 ± 0.4 >100 71.7 ± 26.6 >100 25.6 ± 0.6
a

All chiral N-hydroxythiazole derivatives were prepared as racemic mixtures.

b

Mean average ± SD of two independent experiments (each composed of technical duplicates).

c

Using 0.15 μM FIH, 10.0 μM 2OG and 5.0 μM HIF-1α C-TAD788–822.61

d

Using 0.05 μM His6-AspH315–758, 3.0 μM 2OG and 1.0 μM hFX-CP101–119.58

e

Using 0.15 μM PHD2181–426, 10.0 μM 2OG and 5.0 μM HIF-1α CODD556–574.61

f

Using 0.15 μM KDM4A, 10.0 μM 2OG and 10.0 μM H31–15K9me31–15.69

g

Using 0.15 μM JMJD5, 2.0 μM 2OG and 2.0 μM RSP6128–148.70 Inhibition assays were performed using SPE-MS as described in the ESI.