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.