Chaetocin bears chemical structural similarity to the acetylated histone lysine moiety mimicked by many histone deacetylase inhibitors (HDACIs) and has antimyeloma activity in vitro yet does not appreciably alter levels of acetylated histone H3 in myeloma cells. (A) The chemical structure of chaetocin, indicating similarities to the acetylated histone lysine moiety. (B-C) Effects of chaetocin (24-hour drug exposures) on survival (assessed by trypan blue exclusion) of KAS-6 IL-6–dependent myeloma cells (B) or OCI-MY5 IL-6–independent myeloma cells (C) in vitro. Displayed results are representative of 3 independent experiments. (D) Effects of chaetocin on the cellular levels of acetylated histone H3 in A549 human non–small-cell lung cancer cells. (E) Effects of chaetocin or the known HDACIs aphidicolin, LAQ 824, or trichostatin A on the cellular levels of acetylated histone H3 in U266 human myeloma cells. (D-E) Levels of acetylated histone H3 and actin were assessed using immunoblotting of whole-cell lysates (50 μg total cellular proteins loaded per lane, 24-hour drug exposures).