**3.1 Screening**

There are two fundamental approaches which can be used for the purpose of drug discovery, namely, phenotypic screening and target-based screening.

## **Figure 2.**

*A diagram representing the summary of key notes regarding drug discovery from natural products.*

**131**

**Table 1.**

*Chemical Biology Toolsets for Drug Discovery and Target Identification*

The first one looks at the effects of phenotype that the compound induces on cell, tissue or whole organism, and the second one evaluates the effects of a compound

In the early twentieth century, drug development started with the advancements in pharmacology and synthetic and therapeutic chemistry. In the 1950s and 1960s, enzyme kinetics has provided methods for accurate computation of compound's

Between 1999 and 2008, the US Food and Drug Administration (FDA) approved new drug discovery approaches. During this period, 75 small molecules were discovered and analyzed. Out of these, 28 drugs were discovered through phenotypic

"Alemtuzumab" was the first antibody that was been obtained by using hybridoma technology in combination with phenotypic identification. It was previously reported against relapse of multiple sclerosis and chronic lymphocytic leukemia (CLL). The CD44 antigen (cell surface glycoprotein) antagonist, RG7356, was isolated with the help of function F.I.R.S.T™ platform. Therefore, functional assays antibodies were used to check effects on cell signaling, proliferation, and programmed cell death [19]. Large combinatorial antibody libraries are the sources of human monoclonal antibodies, successfully used in medical and phenotypic screening. For example, BI-505 was isolated by using F.I.R.S.T™ platform. Improved versions of antibodies were ultimately used in simulation studies of tumor cell death assay and for selective B-lymphoma cell surface binding. Soon after the isolation of BI-505, its molecular target was identified as ICAM-1, which were found to be involved in apoptosis of

By using phenotypic screening technology, patients can increase their effective antibody response like B-cell repertoire. For example, from a healthcare worker, anti-respiratory syncytial virus (RSV) antibody, D25, was isolated. On the virus coat, D25 neutralizes RSV, and perfusion structure of the F protein was expressed which was not identified by target-based screening [21]. The use of phenotypic

**duration**

8–10 days [22]

13 days [23]

**References**

selection, and 17 drugs were identified by target dependent selection [18].

B-lymphoma cells. BI-505 has a broad antimyeloma activity [20].

**Disease Cells Assay type Time** 

analyses

Cytochemical and

migration assay

immunohistochemical staining

Immunofluorescence staining for in vitro, Western blot, FACs, ELISA, in vitro biochemical kinase assay,

PC12 Protease release assay 48 hours [26]

Cell viability assay 48 hours [24]

Western blots 18–24 days [25]

RT-PCR assay 48 hours [27]

screening in various experiments is outlined in **Table 1**.

Breast cancer MCF7-RFP

Cystic fibrosis Bronchial

Idiopathic pulmonary fibrosis

Respiratory papillomatosis

Huntington's disease

Familial dysautonomia MDA-RFP

Alveolar epithelial type II cells

Lung tumor cells

epithelial cell

Neural crest precursors

*Phenotypic screening used in some experiments.*

*DOI: http://dx.doi.org/10.5772/intechopen.91732*

effectiveness and enzyme competence [17].

on a purified target protein.

*3.1.1 Phenotypic screening*

The first one looks at the effects of phenotype that the compound induces on cell, tissue or whole organism, and the second one evaluates the effects of a compound on a purified target protein.
