Tubastatin A

Off-white solid. Soluble in DMSO. Cell permeable potent and selective class IIb histone deacetylase 6 (HDAC6) inhibitor (IC50=15nM, >,1000-fold selective against other HDACs and 60-fold for HDAC8), Neuroprotective. Effectively prevents neuronal cell death (by &ge,95% at 10µ,M) upon oxidative stress induction by HCA and selectively induces cellular alpha-tubulin, but not histone H4, hyperacetylation (2.5 to 5µ,M) in primary rat cortical neuron cultures, Improves cognition in Alzheimer's disease transgenic mice, Exhibits cardioprotective and anticancer chemotherapeutic activities. Reduces tumor growth and cell proliferation and induces cell cycle arrest in G1, Inhibits TNFalpha (IC50=272nM) and IL-6 (IC50=712nM) in LPS-stimulated human THP-1 macrophages and displays anti-inflammatory activity in animal models, Antileishmanial, HDAC6 deacetylates tubulin, HSP90 and the core histones (H2A, H2B, H3, H4). Histone deacetylases act via the formation of large multiprotein complexes. HDAC6 plays an important role in microtubule-dependent cell motility, transcriptional regulation, degradation of misfolded proteins and cell cycle and is involved in autophagy, inflammation, cancer and neurodegeneration.