**1.2 Overview of traditional drug discovery method**

The world population is constantly increasing and aging, with a census of close to 8 billion people in 2021 [7]. Additionally, there remains a growing necessity for novel therapeutics to combat the increasing number of cancers, metabolic disorders, infectious diseases, neurodegenerative diseases, and diabetes, as they are a major burden on public health. Despite this necessity, the rate of creation and approval of novel therapeutics is slow by comparison with estimated costs ranging from several hundred million dollars (USD) to several billion per therapeutic with an estimated development time of 12–15 years [8]. The reasons behind these high costs and difficulties with bringing novel therapeutics to market are in some ways straightforward: many projects fail in clinical trials; clinical trials are expensive and time-consuming; therapeutics have failed in the market due to previously unknown public health concerns; research costs are constantly increasing, and the initial investment cost of each therapeutic is high for a pharmaceutical company [9–12]. Traditional drug discovery involves the identification or creation of a new molecular entity (NME). The identification process of an NME usually proceeds as follows: initial basic research generates data supporting inhibition or activation of a protein or pathway that will result in a therapeutic effect in a disease state. Then a lead discovery compound such as a small molecule or biological therapeutic is discovered following some compound screening. The target is validated, and preclinical screening is performed, then the therapeutic can go through clinical trials before filing for drug agencies' approval [11]. The basic steps of this process are illustrated in **Figure 1**. However, at any step of the drug discovery timeline, the therapeutic can fail for a multitude of reasons. Generally, it comes down to two main factors: efficacy and safety [11]. For instance, several therapeutics of AstraZeneca have failed in phase II trials due to toxicological concerns [13]. Other studies stopped clinical trials when the newly developed therapeutics had decreased efficacy compared to existing therapeutics [14]. Furthermore, the time during each of these steps can be lengthy with several years, such as effort needed for compound discovery, clinical development, clinical trials, and FDA or EMA filing (**Figure 1**) [15]. For instance, the overall percent likelihood of approval (LOA) from phase I to approval in all therapeutic fields from 2011 to 2020 was merely about 8% [16]. The LOA differed greatly per therapeutic and per phase (lead compound to phase I, phase I to phase II, etc.). The only step of drug discovery where therapeutics were highly likely to progress was during NDA approval, with a success rate of 80–90% [17]. These

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

#### **Figure 1.**

*Traditional drug discovery process (I) from discovery of target, validation, trials, and FDA/EMA approval with timescale versus repurposing of a market drug (II). This schematic describes the timeline of traditional drug discovery, wherein years of rigorous basic research leads to discovery of a drug, which then undergoes extensive pre-clinical development before going through the clinical trial and market approval phase. With the advent of drug repurposing approach, the timeliness and cost-efficiency of drug discovery significantly improved the driving of a drug for newer indications to the market faster.*

are what led to the long development times for therapeutics discovered through traditional drug discovery methods. In summary, the overall takeaway message is that there is a multitude of factors that can stall drug discovery, and an alternative methodology may be a better approach to bring therapeutics to market.
