Although the mechanism of action is not fully understood, inhibiting HDACs has been observed to result in cell cycle arrest and apoptosis of cancer cells. First HDAC inhibitors have been evaluated in clinical trials and show activity against several cancer diseases. The majority of HDAC inhibitors in and out of clinical trials inhibit all HDAC isoforms nonspecifically (so called pan-inhibitors). Efforts to create selective HDAC inhibitors have seen increased attention over the past several years, leading to several class-selective and some isoform-selective inhibitors.

 

We offer two receptor-based HDAC Targeted Libraries which are specifically targeted towards class I and class II HDAC isoforms in such a way to minimize cross-reactivity between these two classes.

 

 

The selective targeting has been achieved by inspection of HDAC active site’s critical structural determinants for ligand recognition (including essential interaction with Zn²⁺), docking validation of reference set of about 1,000 known HDAC inhibitors with the IC ₅₀  at least 1.1 uM and exclusion of predicted cross-binders from the final set of compounds. Each compound in the library contains a metal-binding moiety that coordinates to the catalytic metal atom (Zn²⁺) within the HDAC active site.

 

The library comprises drug-like compounds only.