Figure 1.

Schematic representation of analogue-sensitive histone demethylase approach. KDM4A, a representative member of the family, demethylates H3K9me3 to H3K9me2 using cofactor 2KG 1 to activate transcription. KDM4A is mutated to carry a ‘hole’ in the pocket while maintaining the catalytic activity. Cofactor-competitive inhibitor carrying complementary steric ‘bump’ specifically inhibits a mutant enzyme. N-oxalylglycine (NOG) 2 serving as inhibitor scaffold because of its structural similarity to 1.