Drug Discovery – Target Identification and Validation

The process of drug development has evolved into an extremely complex procedure. It is estimated that average drug takes 12 years and $270 million from initial discovery to public usage in USA. From thousands of prospective molecules only a handful of drugs undergo clinical studies and even fewer receive market approval.

Discovering a drug

Drug discovery has become the main aim of pharmaceutical industries. Drug Discovery involves finding the target and arriving at the lead. Target refers to the causal agent and Lead refers to the active molecule that interacts with the target. Discovering a drug can be done by two approaches:



Empirical Drug discovery

This is also called as the “black box method”. Thousands of chemical compounds are tested on the disease without knowing the Target.

Rational Drug Discovery

This approach starts from clear knowledge of the Target as well as mechanism by which it is to be attacked.

Process of Drug Discovery

There are five major areas in drug discovery.

Target Identification.

Target Validation.

Lead identification.

Lead Optimization.

Preclinical pharmacology and Toxicology.

Target identification

Identification of potentially suitable target is called Target identification. The approaches of identifying targets include:

Protein expression, Protein biochemistry, Structure function studies, Study of biochemical pathways, High throughput sequence analysis, Positional cloning, Generation of cDNA libraries with ESTs and database mining by sequence homology.

Types of Targets

The targets for the drugs are usually biomolecules such as enzymes, receptors or Ion channels. Once the target is confirmed the modulator for the target is identified. They can be either positive or negative modulators.


Positive modulators

Negative modulators







Ion molecules



List of Positive and negative modulators.

Target Validation

Once the target is identified it has to validated. The process of validation involves extensive testing of the target’s therapeutic potential. A valid target must have a high therapeutic index, that is, a significant therapeutic gain must be predicted trough the use of such a drug.

For Example, A potential anti-bacterial drug can be tested by its effect on growth of the pathogen. If a laboratory animal is susceptible to the disease, compounds can be tested on animals.

Characters of the target

If the target happens to be an enzyme, the following characters are studied: the active sites, amino acids associated in the formation of active site, presence or absence of metal component, number of hydrogen donors and acceptors in the active site.

If the target happens to be a biochemical substance, the following characters are studied: size of the molecule, chemical nature, groups that show hydrogen donor or acceptor capacity, the metaboloic byproducts and how this compound can be modified chemically.


The complex, lengthy and expensive process of drug discovery begins with the identification of the potentially suitable disease target. This proceeds on to the next step which is lead identification.

Source by Suganya R

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