Target Discovery: Identification and Validation

The first stage of drug development is target discovery, also known as target identification and validation, the process of identifying a potential target for a therapeutic drug for a particular disease or condition that does not have a treatment or for which existing therapeutic agents are lacking in some way. Thus, targets may be known, putative, or novel. Proteins are the most common targets and include enzymes, cell signaling receptors, structural proteins, and regulatory factors such as protein kinases. Other targets that are increasingly being investigated include nucleic acids such as mRNA, lipids, and carbohydrates. Show more

There are two main approaches to drug discovery, phenotype-based and target-based. Recently, there has been a resurgence in phenotype-based screening, which is monitoring changes cells in cells, tissues, or organisms. This type of screening has the ability to identify molecules and pathways that were previously not known to be involved in a disease. In target-based screening, each candidate target is validated by numerous experimental methods including modulation of the target to demonstrate that it is directly or indirectly involved in the disease or condition of interest.

In choosing a target, the probability of it being druggable must also be considered; that is, a drug must be able to bind the target and affect its function in a desirable way. Therefore, the target must be accessible to putative therapeutic agents, and the interaction should produce a measurable biological response. There are a wide range of experimental technologies used for validation, with the validation protocols varying depending on the function and characteristics of the target. Show less