Biological target identification and validation are among the most important steps in developing a new drug. Drug target validation involves proving that either DNA, RNA, or a protein molecule is directly involved in a disease process and can be a suitable target for development of a new therapeutic drug.
To qualify as ‘druggable’, a target must be accessible to the proposed drug molecule, and a measurable biological reaction must be provoked as a consequence of the drug interacting with the target. This reaction may be measured both in vitro and in vivo.
Once the target has been identified, for example by genomic or proteomic investigations, the target is then validated in functional studies. The main strategies involved in target validation are gene knockout studies and direct inhibition of the target by small molecules, peptides, antibodies or any other class of inhibitors. The knockout approach genetically inhibits the target, thereby mimicking the action of the drug and allows a drug to be modeled before it is developed.
Information about established drugs and drug-target interactions is available online via public databases such as Drug Bank and the Therapeutic Targets Database. In addition, information on potentially novel drug targets can be found at Center Watch's, Drugs in Clinical Trials Database, which identifies trends in drug development based on current clinical trials.
Examples of popular knockout cell lines for drug target identification and validation
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