What is Compound Screening in Drug Discovery?

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Developing a new medicine and bringing it to market is a long, difficult and expensive process. This process begins with drug discovery:  the unearthing of promising compounds which demonstrate some beneficial biological effect. Compound screening is the primary method by which initial drug discovery is carried out.

Different Approaches to Drug Discovery

In the early days of pharmacology, therapeutic drugs were created from derivatives of traditional medicinal plants: such was the case with aspirin, derived from the bark of the willow tree, and digoxin, which is derived from the foxglove. Other medicines have been discovered “serendipitously” – essentially by accident during scientific research. These include the likes of penicillin, which was first discovered after a staphylococcus culture plate was accidentally contaminated.

Drug discovery has changed since these relatively early findings. Elucidation of the function of cellular receptors, enzymes, and ion channels from the 1960s onward transformed the process of drug discovery into a more rational endeavor: researchers could now work to develop drugs with functional characteristics targeted to specific biological processes.

The completion of the human genome project in 2003 was another significant milestone for drug discovery, enabling scientists to rapidly synthesize large quantities of purified proteins on which to test compounds in a process known as compound screening.

Compound Screening

Dramatic improvements in our understanding of biological processes and the cataloging of millions of pharmacologically active compounds mean that today, drug discovery is typically carried out by testing a large chemical library on biological targets such as cell cultures, enzymes, or proteins and looking for certain effects. This process of compound screening is the first step in modern drug discovery.

Approaches to compound screening can vary. In classical pharmacology (also known as phenotypic drug discovery), researchers use compound screening to find a detectable and desirable change in phenotype – that is, researchers look for a change in the state of a cell culture or entire organism during compound screening.

Other compound screening programs may instead look at the interaction of compounds with individual isolated proteins, which are believed to play an important role in disease progression. This particular compound screening methodology, known as reverse pharmacology or target-based drug discovery, is the most widely used method of drug discovery today.

How is Compound Screening Carried Out?

Compound screening facilities typically hold a library of “stock plates” – grids of small wells which contain meticulously cataloged chemical compounds for testing.

Compound screening typically takes place on an assay plate. This is essentially a copy of the stock plate, with each well containing a small sample (often nanoliter scale) of a compound taken from a corresponding well on the stock plate. The compound screening process begins when a biological target (e.g., protein, cells, or animal embryo) is added to each well of the assay plate. After an incubation period, measurements can be taken to ascertain the effects of each test compound on the biological targets.

Measurements in compound screening may be taken manually, e.g., by microscopy, or automated measurements of quantities such as luminescence or absorbance may be taken.

In this way, compound screening enables those compounds which produce positive results – known as “hits” – to be identified and the rest to be discarded. Once this is done, the process of further testing and drug development can begin.

Platypus Technologies provides a full suite of products for compound screening and biological assays, including the Oris™: a 96-well cell migration assay platform that uses stopper barriers to create a central cell-free detection zone. To find out more about our range of products, get in touch with us today.