HDAC

About

Technology Histone acetylation and deacetylation are important in chromatin folding and maintenance. HDACs are also involved in the reversible acetylation of non-histone proteins. Altered HDAC activities are present in many types of cancers and as a result are an attractive therapeutic target for drug discovery. Georgetown University is seeking a partner interested in the development and commercialization of novel HDAC inhibitors. Dr. Mira Jung and colleagues have discovered compounds and derivatives that are effective in sensitizing cancer cells as well as enhancing the cytotoxic effects of radiotherapy. The HDAC inhibitors may also be used for the treatment of neurodegenerative diseases. Several of the compounds show 50% HDAC inhibition at nanomolar concentrations. Development stage Rational design was used to guide the synthesis of mercaptoacetamide and hydroxyamide-based compounds to be used as HDAC inhibitors. The compounds were tested on radiation-resistant cancer cell lines for the initial radiosensitization experiments. In cells pretreated with the compounds, the radiation dose required was decreased by 33% compared to non-treated controls. In vitro assays demonstrated that several of the compounds were effective and inhibiting 50% HDAC activity at low nanomolar concentrations. Administration of the representative compounds of each class led to tumor regression in mouse models. Key experiments that need to be performed include: 1) testing the effects of the compounds, including toxicity and stability studies, in large animals and 2) determining compound efficacy on three additional cancer cell lines.