Description
InformationTubastatin A is a potent and selectiveHDAC6inhibitor withIC50of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotesautophagyand increasesapoptosis.TargetsHDAC6 (Cell-free assay) 15 nMIn vitroTubastatin A is selective at all isozymes except HDAC8 and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. Tubastatin A preferentially induces α-tubulin hyperacetylation at 2.5 µM. Slight induction of histone hyperacetylation is seen for Tubastatin A at 10 µM. Tubastatin A displays dose-dependent protection against homocysteic acid-induced neuronal cell death starting at 5 µM with near complete protection at 10 µM. Tubastatin A (10 µM) induces an increase in acetylated-α-tubulin levels and the restoration of primary cilia expression in the cholangiocarcinoma cell lines (18-fold); and the restoration of primary cilia correlated with downregulated Hedgehog (Hh) and MAPK signaling pathways, as well as decreased cell proliferation rates (in average by 50%) and invasion (by 40%). Tubastatin A shows significant inhibition of TNF-α and IL-6 in LPS stimulated human THP-1 macrophages with an IC50 of 272 nM and 712 nM. Tubastatin A inhibits nitric oxide (NO) secretion in murine Raw 264.7 macrophages dose depenndently with an IC50 of 4.2 µM.In vivoTubastatin A reduces the growth of cholangiocarcinoma in vivo. Tubastatin A (10 mg/kg) induces a 6-fold lower mean tumor weights in syngeneic rat orthotopic model of cholangiocarcinoma, and reduction of the ratios of tumor weight to liver weight and body weight (5- and 5.6-fold, respectively), as well as a greater frequency of ciliated cholangiocytes compared with controls (29% vs 1.4%). Tubastatin A significantly decreases the amount of PCNA-positive cells in the treated tumors compared with vehicle controls (34% vs 65%). Tubastat A shows significant inhibition of paw volume at 30 mg/kg i.p. in a Freund\'s complete adjuvant (FCA) induced animal model of inflammation. Tubastat A (30 mg/kg i.p.) significant attenuates clinical scores (~ 70%), and IL-6 expression in paw tissues of collagen induced arthritis DBA1 mouse.Cell Research(from reference)Cell lines：Human cholangiocarcinoma cell lines HuCCT-1 Concentrations：~10 µM Incubation Time：21 days Application：Tubastatin A hydrochloride may be used in HDAC6-mediated cell signaling studies