**2. Approaches for drug repurposing**

In drug repurposing, three major steps are involved which consist of (i) identification of target candidate for new indication (generation of new hypothesis for new indication or new target), (ii) exploration of mechanism or signaling pathway involved in drug or disease and (iii) finally proving the efficacy of drug in phase 2 and 3 clinical trials. Among all steps, identification of lead candidate is one of the most critical steps. This is the step where the most sophisticated and systematic approaches are needed to be implicated for generation of new hypothesis in drug repurposing. Drugs can be repurposed via multiple ways which may be either experimentally, clinical based or computationally (**Figure 3**). Computational approach is '*in silico*' based drug repurposing which is further subclassified as either drug-centric or disease-centric. In drug-centric, we find new indications for existing drugs while in disease-centric approach, we try new drugs for an existing disease.

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*Drug Repurposing and Orphan Disease Therapeutics DOI: http://dx.doi.org/10.5772/intechopen.91941*

**2.1 Experimental strategies in drug repurposing**

kinases which may be treated as possible targets of gefitinib [14].

Techniques like chromatography and mass spectrometry are being used to find all possible binding targets of drug candidates. Brehmer et al. conducted a study using HeLa cell extract to identify possible protein targets of gefitinib. The results of mass spectrometry revealed that the drug can interact with 20 different protein

*Approaches for drug repurposing. (a) Experimental based, (b) clinical based and (c) computational based* 

In the world of drug discovery and development, the term phenotyping screening is used to describe the ways adopted to identify the biological effects of a drug which is either directly or indirectly linked to a disease. With the development of robotic and sensitive screening tools, the approach is used to screen thousands of chemical drug libraries in a single go. It involves the screening of target drug candidates either using cell-based screens (high throughput screening (HTS)) or even whole organism [15]. Cell based assays involve cell lines derived from human or animals, immortalized cell lines or induced pluripotent cells lines (iPSCs), etc. For example, Iljin et al. [16] performed HTS of approximately 5000 small molecules using prostate cancer epithelial cell lines. In this experiment, disulfiram was found to possess selective antineoplastic property which was validated later using genome wide gene expression studies [16]. Important cell-based assays that are being performed in drug discovery and repurposing include: cell viability assay, signaling pathways assay and disease related mechanistic assay. Other cell assays

*2.1.1 Binding assays to identify target candidate*

*2.1.2 Phenotyping screening*

**Figure 3.**

*drug repurposing.*

*Drug Repurposing and Orphan Disease Therapeutics DOI: http://dx.doi.org/10.5772/intechopen.91941*

**Figure 3.**

*Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications*

repurposing provides one of the best faster and economical ways to find new treatment options in ODs (**Figure 2**). To facilitate drug development and treatment options in orphan disease management FDA Orphan Drug Act (ODA) 1983, has provided many of the benefits or incentives to pharmaceutical and research companies including (i) tax credits (ii) clinical research aids, (iii) fast-track marketing authorization procedures (FDA approval), and (iv) marketing

In drug repurposing, three major steps are involved which consist of (i) identification of target candidate for new indication (generation of new hypothesis for new indication or new target), (ii) exploration of mechanism or signaling pathway involved in drug or disease and (iii) finally proving the efficacy of drug in phase 2 and 3 clinical trials. Among all steps, identification of lead candidate is one of the most critical steps. This is the step where the most sophisticated and systematic approaches are needed to be implicated for generation of new hypothesis in drug repurposing. Drugs can be repurposed via multiple ways which may be either experimentally, clinical based or computationally (**Figure 3**). Computational approach is '*in silico*' based drug repurposing which is further subclassified as either drug-centric or disease-centric. In drug-centric, we find new indications for existing drugs while in disease-centric approach, we try new drugs for an

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existing disease.

exclusivity [13].

**Figure 2.**

**2. Approaches for drug repurposing**

*Resource database for orphan diseases (ODs) and drugs.*

*Approaches for drug repurposing. (a) Experimental based, (b) clinical based and (c) computational based drug repurposing.*
