Exploration of hydrazine-based small molecules as metal chelators for KDM4 inhibition.

ABSTRACT: Hydrazines and related moieties are frequently employed in inhibitory compounds targeting iron-dependent dioxygenases such as the histone lysine demethylases (KDMs), which are promising targets in targeted epigenetic cancer therapies. Four compound libraries consisting of 81 compounds were synthesized and screened for inhibitory activity against KDM4A in an optimised AlphaScreen assay. Slight inhibition was observed for the series of 3-((2-benzoylhydrazono)methyl)benzoic acids that constituted library 1, with compounds 16, 17, 24, 28, and 38 exhibiting the most significant reductions in KDM4A activity at a screening concentration of 20 μM. Removal of the hydrazide carbonyl to generate a series of 3-((2-hydrazono)methyl)benzoic acids in library 2 proved detrimental to inhibitory activity ex

SUBMITTER: Saxton AJ 

PROVIDER: S-EPMC12243619 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature