Tubacin is a highly potent and selective, reversible, cell-permeable inhibitor of HDAC6 with an IC50 value of 4 nM. Tubacin inhibits α- tubulin deacetylation in mammalian cells. Tubacin is specific for the tubulin deacetylase activity of HDAC6. The effects of tubacin has been studied in hematologic malignancies, such as multiple myeloma and leukemia cell lines. Overexpression of HDAC6 in primary lymphocytes and T cell lines increase cell migration in response to cytokines. Knockdown of HDAC6 in T cells decreased chemotactic mobility independent of its enzymatic activity. Furthermore, treatment of multiple myeloma cells with tubacin resulted in decreased cell growth at an IC50 of 2–5uM. In terms of toxicity to normal bone marrow and blood cells, treatment of peripheral blood mononuclear cells (PBMC) and bone marrow progenitor cells (BMPC) with tubacin (5uM) for 12 hours showed that constitutive expression of HDAC6 is higher in BMPCs than PBMCs. Furthermore, acetylation of α-tubulin was markedly enhanced by tubacin in BMPCs but not in PBMCs. Bortezomib and tubacin together induced synergistic antitumor activity in multiple myeloma cells and primary bone marrow plasma cells. Published data therefore provide support for combined therapy in clinical trials for patients with multiple myeloma.