Harvard University and Dana-Farber Cancer Institute have inked an exclusive therapeutic license with Boston-based Acetylon Pharmaceuticals for a platform technology and chemical methodology to conduct high-throughput screening and lead optimization for histone deacetylase (HDAC) inhibitor compounds and a portfolio of small-molecule selective HDAC enzyme inhibitors. The licensed technology includes the first-ever selective inhibitor of HDAC6, a Class IIB enzyme that has emerged as an important target in inflammatory disease, neurologic disease, and cancer. Acetylon is developing potential drug candidates based on Class II-selective HDAC inhibitors. The company believes that its selective HDAC inhibitor compounds may enhance clinical utility by reducing or eliminating the side effects associated with existing non-selective HDAC inhibitors. The platform and methodology were discovered by two of Acetylon’s scientific founders, James E. Bradner, MD, assistant professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, and Ralph Mazitschek, PhD, instructor in chemical biology at Harvard Medical School and the Massachusetts General Hospital, and colleagues. They described the technology in Nature Chemical Biology.
Acetylon’s lead HDAC6 inhibitor program is focused on enhancing drug potency and reducing or eliminating side effects common to HDAC inhibition through selective targeting of the HDAC6 enzyme. Inhibition of HDAC6 versus other isoforms preserves normal gene expression in cells, thereby minimizing patient toxicity. At the same time, HDAC6 inhibition severely disrupts the ability of diseased cells to produce normal proteins and to dispose of damaged, misfolded proteins. Since metabolically active cancer and autoimmune cells produce large amounts of misfolded proteins, inhibition of HDAC6 results in further increased generation and accumulation of protein “trash,” triggering self-destruction of diseased cells via programmed cell death and leading to regression of disease. The Harvard/Dana-Farber drug discovery and development tools “open new doors to expand our Class II-selective HDAC inhibitors program,” says Walter Ogier, CEO of Acetylon.
Source: Earth Times