Histone deacetylases (HDACs) catalyze the hydrolytic removal of acetyl groups from histone lysine residues, which commonly results in chromatin condensation and transcriptional repression. LMK 235 is an HDAC inhibitor that selectively targets HDACs 4 and 5 (IC50s = 12 and 4 nM, respectively) over other HDACs (IC50s = 56, 320, 850, 880, and 1,280 for HDACs 6, 1, 11, 2, and 8, respectively). It displays enhanced cytotoxic effects against human cancer cell lines, compared to SAHA or trichostatin A . LMK 235 and derivatives inhibit the growth of the malarial parasite P. falciparum at multiple life cycle stages at nanomolar concentrations.
