**4. Metabolomics in the drug discovery and development**

Drug research has become increasingly expensive, challenging, and risky over the previous two decades. The costs of research and development have risen, as has the cost of bringing a novel medicine through all stages of testing, which has a direct impact on the frequency with which a new drug is launched to the market. This is because pharmaceutical companies are unable to identify the therapeutic target or because of the multiple targets in case of complicated diseases such as cancer, heart disease, obesity, Alzheimer's disease etc. Another key issue is that the rate of converting a promising lead to a drug is decreasing; just one out of every thirty lead compounds reaches phase-I clinical trials, and only one out of every six drugs crosses clinical trials and enters the market. Still, there is a 5% chance that the drug may be withdrawn from the market due to adverse occurrences. Such failures can be costly for pharmaceutical corporations, affecting drug pricing directly. These failures can be addressed or reduced by strengthening drug target screening, tracking drug toxicity in the preclinical or developmental stage, and monitoring and reporting ADRs during the prescription or physician stage. Metabolomics, an emerging discipline of Omics science, can help to mitigate such failures and accelerate the drug discovery process [33–35]. In recent development ADME studies are commonly employed in drug discovery to optimize the balance of attributes required to turn leads into safe drugs. Metabolite characterization has recently emerged as a key driver in the drug discovery process, assisting in the optimisation of ADME characteristics and increasing drug success rates. For decades, it has been a valuable and important aspect of the drug development process. Over the last decade, there has been an increased effort to solve metabolic concerns using high throughput technologies for screening compounds, which has resulted in a strong need for more quick approaches for metabolite identification [7]. It has been discovered that metabolomics can provide drug researchers and regulators with an efficient and cost-effective method for discovering and developing viable medicinal products (**Figure 3**).

Metabolomics could aid in the following areas of drug discovery and development process:

#### **4.1 Lead compound identification**

Metabolomics, natural product chemistry and synthetic medicinal chemistry mainly focusses on the identification and characterization of small molecules as maximum of the FDA approved drugs are small molecules with a molecular weight (≤1500 Da) [37]. It is estimated that majority of these approved drugs are of preexisting metabolites or preexisting natural product in nature (few examples such as


#### **Figure 3.**

 *Application of metabolomics in drug discovery and development [ 36 ].* 

corticosteroids and their derivatives to treat inflammation, ascorbic acid from citrus fruit to treat scurvy, quinine from cinchona tree to treat malaria, paclitaxel from yew bark to treat breast cancer etc.).It has been observed that small molecules are cofactors or substrates for at least one third of human proteins, hence identifying the unexplored ones from plant and human could become an excellent source for new drug candidates or drug scaffolds. Combination of experimental, computational and bibliographic surveys are underway to identify and characterize new or little-known metabolites that plays important roles in cell physiology, enzymatic activity, stress response and disease [ 38 , 39 ]. Prior metabolite knowledge about known or hypothetical compounds is used in conjunction with NMR or MS data to identify novel compounds which are similar to currently available molecules. More than 20 million NMR and MS libraries of compounds are now available online can have impact on identification of new metabolite [ 40 ].
