Fig 1: Concept to merge the scaffolds of PCI‐34051 and Tubastatin A. Top: PCI‐34051 (left) and Tubastatin A (right) are depicted with their zinc binding groups (ZBG) in red, linkers in blue, and cap groups in orange. Recognition that both inhibitors share an N‐benzylindole scaffold inspired the design of hybrid inhibitors (center) with two ZBGs (red) and a central core that would function as both cap group and linker (green). Lower left and right: Inhibition of HDAC8 and HDAC6/10 would result from engagement of one of the two ZBGs. Lower center: Synthesized mono‐ and hybrid dihydroxamic acids used in this study.
Fig 2: Docking pose for panobinostat and panobinostat derivatives in the HDAC8 receptor. (a) Overlay of all compounds investigated in this study in the HDAC8 active site: panobinostat (green), TOI1 (purple), TOI2 (yellow) and TOI4 (grey); (b) TOI3-rev (pink) docking pose in active site; (c) TOI4 (grey) docking pose in the active site.
Supplier Page from BPS Bioscience, Inc. for HDAC8, His-Tag Recombinant