IOX4 is a potent PHD2 inhibitor (IC50 = 1.6 nM)

PHD2:1.6 nM

IOX4 as a highly potent and selective inhibitor of human PHD2, As shown by studies with mice, IOX4 is useful for in vivo work;?it will then be useful for investigations on the suitability of the PHDs as targets for cerebral diseases such as stroke.?The combined kinetic and biophysical analyses reveal that IOX4 (and IOX2) compete with 2OG for binding to PHD2;?the triazole rings of the inhibitors bind in the pocket occupied by the CH2CH2COOH side chain of 2OG.?The results thus reveal the potential of non-acid containing PHD inhibitors—an important finding given the potential of HIFα upregulation mediated by PHD inhibition in the treatment of stroke, as acids do not often permeate the blood-brain barrier efficiently[1].