FLUOR DE LYS^® HDAC6 fluorometric drug discovery kit

• Useful for inhibitor screening or characterizing enzyme kinetics
• Includes optimal substrate selected from a panel of acetylated sites in p53 and histones
• Supplied with enough recombinant enzyme for 96 assays (1 x 96-well plate)

A FLUOR DE LYS^® fluorescent assay system. The HDAC6 Fluorescent Activity Assay/Drug Discovery Kit is a complete assay system designed to measure the lysyl deacetylase activity of the recombinant human HDAC6 included in the kit. The kit is ideal for chemical library screening for candidate inhibitors or activators or kinetic assay of the enzyme under varying conditions. The FLUOR DE LYS^® HDAC6 assay is based on the FLUOR DE LYS^® Substrate and FLUOR DE LYS^® Developer combination. The assay procedure has two steps. First, the FLUOR DE LYS^® Substrate, which comprises an acetylated lysine side chain, is incubated with HDAC6. Deacetylation of the substrate sensitizes the substrate so that, in the second step, treatment with the FLUOR DE LYS^®Developer produces a fluorophore.

HDAC6 is a class II HDAC, a group defined by its member’s homology to the yeast HDAC. HDAC6 falls into the class IIb subclass, along with HDAC10, but is unique among human HDACs in that it contains two full deacetylase domains. Primarily located to cytoplasm, HDAC6 is a tubulin deacetylase. Other HDAC6 substrates include Hsp90, cortactin and peroxiredoxins. Through these deacetylase activities and its ubiquitin and other binding activities, HDAC6 plays key regulatory roles in cell motility, protein folding, the ubiquitin-proteasome pathway, the aggresome pathway and autophagy, suggesting a central function in the coordination of cellular stress responses. HDAC6 is required for efficient oncogenic tumorigenesis. The mechanisms underlying this requirement may include HDAC6-mediated promotion of invasive cell motility, resistance to anoikis, removal of toxic misfolded proteins, inhibition of Hsp90 stabilization of metastasis suppressors and promotion of angiogenesis. HDAC6 null-mice, while outwardly normal, have increased resistance to chemical carcinogenesis. It is thus reasonable to suppose that HDAC6 inhibition may be a key factor in the anti-cancer effects of pan-HDAC inhibitors and that selective HDAC6 inhibitors may have the potential for greater effectiveness and reduced side-effects.