Epigenetics and Novel Therapeutic Targets

Epigenetics concerns the cellular processes associated with modification of chromatin that lead to differential gene expression. It helps explain why different cells in the body develop to fulfil specialised functions, despite containing identical DNA information.

Errors in epigenetic mechanisms result in aberrant cellular behaviour and can lead to the development of cancer, neurodegenerative diseases, metabolic disorders and inflammatory diseases.

Initial epigenetic drug discovery has centred on inhibition of DNA methyltransferases and histone deacetylases, mainly for cancer treatment. Positive clinical effects have fuelled an active search for further epigenetic targets with clear modes of action, and potentially greater effectiveness in treating disease, either as single agents or in combinations with other drugs.

Such second generation targets are predominantly enzymes that modify histones, the main protein associated with DNA in the chromatin complex. These include histone demethylases, acetyltransferases, methyltransferases, ubiquitin ligases, deubiquitinases, phosphatases, clippases, SUMOylators and oxidases. Other classes of target include DNA demethylases and RNA related targets.  

CellCentric has prioritised specific histone modifying enzymes for focused drug discovery where the company:

• has an understanding of mechanism of action
• knows that it is possible to generate small molecule inhibitors
• has data to support relevance of the target to specific cancer patient populations