Not all proposed family members are shown. Each demethylation reaction is coupled to 2OG decarboxylation and formaldehyde production. KIAA1718 has recently been assigned as KDM7A, however its JmjC domain shows high sequence and structural similarity with the KDM2 subfamily members.

Daminozide 19 is selective for KDM2A. Tricarboxylic acid cycle intermediates succinate 1 and fumarate 2 were generally poor demethylase inhibitors, though KDM4E was an exception to this trend. (R)- and (S)-2-hydroxyglutarate enantiomers, produced by gain-of-function mutations to isocitrate dehydrogenase were inhibitors of the KDM2, KDM3 and KDM4 histone demethylases. The catechols 16 and 17, bipyridyl 18 and 8-hydroxyquinoline 21 inhibited all demethylases screened. By contrast, 5 most potently inhibited PHD2 (prolyl hydroxylase domain enzyme isoform 2). Each compound was screened in an AlphaScreen assay and is represented as % inhibition of the enzyme at 20 μM compound. Details of the assays are in the .

Inhibition of KDM2A by daminozide is competitive with 2OG but not peptide substrate.

PHF8 (with Zn(II) substituting for Fe(II),) and KDM4A (with Ni(II) substituting for Fe(II)) and FIH (with Zn(II) substituting for Fe(II)) (). Daminozide binds the metal through its hydrazide amine lone pair and carbonyl oxygen. Two distinct orientations of daminozide are observed in the two KDM4A molecules in the asymmetric unit; both are shown (see for electron density maps). Selectivity of daminozide for the KDM2/7 subfamily may arise because they possess a hydrophobic region (Tyr257, Val255 and Ile313) into which the two daminozide methyl groups may bind. In contrast, the equivalent regions of KDM4A, FIH and the other tested demethylases/oxygenases are more hydrophilic.