Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM, approximately 350-fold selectivity over HDAC1.

HDAC6 (cell-free assay):4nM

Tubacin不直接稳定微管，通过提高A549细胞中α-微管蛋白乙酰化水平（EC50为2.5μM）发挥作用。Tubacin抑制HDAC6介导的α-微管蛋白去乙酰化作用，并能阻止野生型及HDAC6过表达细胞的迁移。与紫杉醇联合使用时，Tubacin可协同增强微管蛋白乙酰化。同时，Tubacin显著抑制药物敏感和药物抗性多发性骨髓瘤(MM)细胞增长（IC50为5–20μM），并通过激活caspases诱导细胞凋亡。

在鸡胚中，Tubacin抑制HDAC6的活性可以减少在matrigel/尼龙网中新血管的形成。在小鼠体内植入的血管生成器中，Tubacin同样阻碍了新血管的形成。

Enzyme Inhibition Assay:Enzyme inhibition assays are performed using the Reaction Biology HDAC Spectrum platform. The HDAC1, 2, 4, 5, 6, 7, 8, 9, 10, and 11 assays used isolated recombinant human protein; HDAC3/NcoR2 complex is used for the HDAC3 assay. Substrate for HDAC1, 2, 3, 6, 10, and 11 assays is a fluorogenic peptide from p53 residues 379-382 (RHKKAc); substrate for HDAC8 is fluorogenic diacyl peptide based on residues 379-382 of p53 (RHKAcKAc). Acetyl-Lys(trifluoroacetyl)-AMC substrate is used for HDAC4, 5, 7, and 9 assays. Compounds are dissolved in DMSO and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 30 μM. Control Compound Trichostatin A (TSA) is tested in a 10-dose IC50 with 3-fold serial dilution starting at 5 μM. IC50 values are extracted by curve-fitting the dose/response slopes.

Cell lines: Drug-sensitive (MM.1S,U266,INA-6,and RPMI8226) and drug-resistant (RPMI-LR5 and RPMI-Dox40) MM cell lines. Concentrations: ~20 μM. Incubation Time: 72 hours. Method:The inhibitory effect of bortezomib and/or tubacin on MM cell growth is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye absorbance.All experiments are performed in quadruplicate.

Animal Models: Athymic nude mice implanted with angioreactorsFormulation: DMSODosages: --Administration: Tubacin is filled in semiclosed angioreactors, and then implanted into the mice.