Histones are proteins that associate with DNA and play an important role in gene regulation and DNA replication. Histone deacetylases, also known as HDACs, are a family of enzymes that remove acetal groups from histones and cytoplasmic proteins to regulate gene transcription and protein activity, respectively. Unlike normal cells, cancer cells may lack multiple epigenetic regulatory mechanisms and therefore, when HDACs are inhibited, it results in tumor cell cycle arrest, differentiation and apoptosis.
Bocodepsin specifically inhibits Class I HDACs and causes the hyperacetylation of histones. This over acetylation activates transcription and triggers the production of proteins that have been downregulated. Importantly, many of these down-regulation events are used by cancer cells to escape from anti-cancer therapy. Thus, combining bocodepsin with targeted therapies is predicted to be more effective than using those therapies in isolation.