Identification of novel small-molecule histone deacetylase inhibitors by medium-throughput screening using a fluorigenic assay.

摘要: HDACs (histone deacetylases) are considered to be among the most important enzymes that regulate gene expression in eukaryotic cells. In general, increased levels of histone acetylation associated with transcriptional activity, whereas decreased linked repression expression. associate a number cellular oncogenes and tumour-suppressor genes, leading an aberrant recruitment HDAC which results changes expression, impaired differentiation excessive proliferation tumour Therefore inhibitors efficient anti-proliferative agents both vitro vivo pre-clinical models cancer, making them promising anticancer therapeutics. present paper, we medium-throughput screening programme aiming at identification novel using HDAH (HDAC-like amidohydrolase) from Bordetella or Alcaligenes strain FB188 as model enzyme. Within library 3719 compounds, several new classes inhibitor were identified. Among these hit there also potent HDACs, demonstrated by increase H4 acetylation, accompanied decrease cell metabolism SHEP neuroblastoma T24 bladder carcinoma conclusion, compound enzyme identified lead structures for further development.