Therapeutics: Histone deacetylase 6 (HDAC6)

In vitro and mouse studies identified an HDAC6 inhibitor that could help treat cancer. Chemical synthesis and in vitro testing of 3-aminopyrrolidinone-based hydroxamic acid analogs identified a lead compound that inhibited HDAC6 with an IC50 of 17nM. In a human multiple myeloma (MM) cell line, the compound induced tubulin acetylation - which destabilize microtubules - with an EC50 of 300 nM and increased cell death compared with vehicle. In mice, the fraction of lead compound reaching plasma after oral administration was 55% compared with 8% for the pan-HDAC inhibitor vorinostat. Next steps could include testing in animal models of various cancers...