TH34 is a novel, potent and selective HDAC6/8/10 (histone deacetylase) inhibitor for neuroblastoma therapy. It shows pronounced selectivity for HDACs 6, 8 and 10 over HDACs 1, 2 and 3. TH34 exhibits strong binding activity against HDAC6, 8, and 10 in a NanoBRET assay, with low-micromolar IC50 concentrations (HDAC6: 4.6 µM, HDAC8: 1.9 µM, and HDAC10: 7.7 µM). The most frequent extracranial solid tumor in children, neuroblastoma, has been found to be associated with exceptionally poor outcomes when high levels of HDAC 8 and HDAC10 expression are present. In vitro neuroblast maturation is induced by HDAC8 inhibition, and in vivo neuroblastoma xenograft growth is inhibited by retinoic acid treatment in concert. In cultured neuroblastoma cells, HDAC10 inhibition causes lysosomal homeostasis to be disrupted, which in turn causes an increase in the intracellular accumulation of chemotherapeutics and ultimately results in cell death. As of yet, no HDAC inhibitor has been reported that can inhibit HDACs 1, 2, and 3 while simultaneously covering HDAC8 and HDAC10 at micromolar concentrations. At concentrations up to 25 µM, TH34 is well-tolerated by non-transformed human skin fibroblasts and only slightly inhibits colony growth in medulloblastoma cell lines. However, in several human neuroblastoma cell lines, it specifically causes caspase-dependent programmed cell death in a concentration-dependent manner. HDAC6/8/10 inhibition causes cell-cycle arrest and mitotic aberrations in addition to inducing DNA double-strand breaks. When TH34 treatment is continued, neuroblastoma cells show increased levels of neuronal differentiation markers, which is reflected in the development of neurite-like outgrowths. After receiving treatment for a long time, all neuroblastoma cells eventually die. When TH34 and plasma-achievable doses of retinoic acid, a medication used in neuroblastoma treatment, are combined, they work together to inhibit colony growth (combination index (CI).

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.