Epigenetic drug discovery and tools
 

Epigenetics and Novel Therapeutic Targets

Epigenetics is a rapidly expanding area of research whose importance for the generation of novel therapeutics is becoming increasingly apparent. It concerns the cellular processes associated with chromatin* that lead to differential gene expression and explains how 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, inflammatory diseases, cardiac disorders, neurodegenerative diseases and diabetes.  In the field of cancer for example, it is now well documented that the majority of tumour cells display abnormal epigenetic patterns. Two classes of anti-cancer drug have a predominately epigenetic mode of action.
 
As the complexity of epigenetic control becomes clearer, it is evident that there are literally hundreds of potential epigenetic enzyme targets that are relevant for the development of small molecule drugs.  In addition, manipulation of epigenetic processes and pathways is important in regenerative medicine applications.

 

Novel Targets beyond DNMTs and HDACs

There are currently two therapeutic classes of drugs targeting epigenetic mechanisms (DNA methyltransferase and histone deacetylase inhibitors) and although these clearly demonstrate the therapeutic relevance of epigenetic targets, as with other pioneer achievements, they are most unlikely to represent the best the field can offer.
 
Of the hundreds of enzymes that have a direct or indirect impact on chromatin and gene expression, many are inappropriately expressed in disease conditions and therefore represent drug target candidates. 
 
This is CellCentric’s focus  – using the breadth of it epigenetics platform to identify novel drug targets to fuel the company’s proprietary drug discovery portfolio.

 

The company has multiple small molecule therapeutic discovery programmes across a range of enzyme classes, including demethylases, methyltransferases and ubiquitin modulators.
 


*Chromatin is the complex combination of DNA, RNA, and protein that makes up chromosomes

  

Reprogramming

Understanding epigenetic processes in both disease and natural development (embryogenesis), is key to identifying novel targets and understanding their mechanism of action. CellCentric coordinates a number of direct research efforts in the area of cellular reprogramming; where cell fate is altered through epigenetic change.
 
CellCentric’s scientific founder, Prof Azim Surani is the pioneer who demonstrated that cell function can be made to change through modifying epigenetic processes, and that stem cell-like qualities can be induced through epigenetic imprint erasure. In addition to cellular reprogramming, this type of knowledge has particular importance when considering novel targets to address proliferative and intractable tumour cell populations, sometimes known as cancer stem cells.