**4. Recent advances in drug repurposing for epigenetic-based therapy**

Repurposing drugs for epigenetic-based therapy is a newly emerging field with significant potential for the development of drugs for diseases with high incidences, such as cancer and cardiovascular diseases. Notably, epigenetic enzymes play a critical role in the molecular pathology of the diseases discussed in this chapter. Thus, it is important to increase the development of drugs targeting epigenetic enzymes in a timely and cost-efficient manner. Due to the increased development of HTS methods, availability of comprehensive omics data, and advances in computational tools, the use of drug repurposing as a therapeutic strategy is highly promising. Through literature database search, researchers can often extrapolate the potential efficacy of a market-approved drug in a new indication based on the drug's molecular effect and cellular impact in an older indication. Such information opens a window of opportunity to examine the use of market-approved drugs in a new indication. For example, researchers observed that artemisinin, an approved malaria drug derived from the wormwood plant, forms free radicals with iron. Considering that increased iron levels are a well-established risk factor for breast cancer development, an investigation was launched into the anti-cancer effects of artemisinin [82]. Moreover, recent studies in epigenetic-based therapy have also adopted molecular docking tools to identify valuable drug candidates that can be repurposed for new indications [94, 108]. The study of the target structure and ligand interaction significantly scales down the evaluation of drugs that are unlikely to bind to the epigenetic targets that fuel a disease progression. This approach also leverages structural similarities of a market-approved drug's target to discover potential newer indications. Notably, our group developed an AlphaLISA-based high-throughput screen (HTS) that aided the identification of promising market-approved drug candidates which targets PRMT5. This unique HTS method allowed us to preclinically investigate the efficacy of candesartan and cloperastine, a hypertensive and cold medicine, respectively, in several solid cancers [87, 88]. As with other drug discovery approaches, the exciting advances in targeting epigenetic enzymes with market-approved drugs can be improved with additional extensive research on various aspects of the drug's molecular mechanisms. In some cases, although a

*Repurposing Market Drugs to Target Epigenetic Enzymes in Human Diseases DOI: http://dx.doi.org/10.5772/intechopen.101397*

repurposed drug is known to have an epigenetic effect, its primary molecular target is not always clear. This gap creates an avenue for the possibility of off-target effects that may be adverse in newer indications. Similarly, the challenges with false-positive results in HTS can be surmounted by incorporating the dose-response factor as a critical variable for understanding a market-approved drugs' efficacy against an epigenetic target. Also, considering that the function of a market-approved drug can be context-dependent, it is critical to pursue new indications known to be highly driven by an epigenetic target of interest. Collectively, addressing the gaps in molecular mechanisms that drive disease pathology and improving existing screening methods will significantly advance the field of epigenetic-based therapy using market-approved drugs.
