Skip to main content
. 2022 Jul 11;88(12):5238–5256. doi: 10.1111/bcp.15428

FIGURE 1.

FIGURE 1

ESM‐HDAC391 demonstrates myeloid‐targeted histone deacetylase (HDAC) inhibitory effects in vitro. (A) Schematic of ESM targeting, showing conversion of ester ESM‐HDAC391 to acid HDAC189 in carboxylesterase‐1‐expressing cells in comparison to the non‐hydrolysable control molecule HDAC935. The HDACi pharmacophore is shown in purple and the linked ester/acid moieties are shown in orange. (B, C) Inhibition of HeLa nuclear extract HDAC activity by ESM‐HDAC391 (n = 6) and HDAC189 (n = 2), respectively. (D, E) Acetylation of leucocyte populations in human whole blood following 4 hours incubation with ESM‐HDAC391 (n = 13) and HDAC935 (n = 4), respectively. (F) Inhibition of Tumour Necrosis Factor‐α (TNF‐α) production in lipopolysaccharide‐stimulated blood by ESM‐HDAC391 and HDAC935 (n = 4). (G) Quantification of HDAC189 levels in isolated monocytes following incubation of blood with ESM‐HDAC391 for 1 or 6 hours (n = 3), with each donor plotted separately