Polypharmacology: the future of drug discovery?

By , BPharm

Polypharmacology involves the pharmaceutical compounds that exert an effect on multiple targets in the body.

There is currently significant interest in this area of research for drug discovery in the future, due to the projected ability to improve efficacy and reduce drug resistance. However, there is some concern about the adverse effects that may be observed with polypharmacological treatments.

Polypharmacology refers to a single drug that acts on multiple targets, which may be associated with a single disease pathway or several different disease pathways. This approach also utilizes drug repurposing, which involves the discovery of unknown secondary targets of existing drugs and integrating this knowledge into practice.

Current Examples in Practice

There are several examples of this phenomenon already commonly in use. For example, aspirin is usually recommended to relieve pain or reduce fever, but it also has an effect on inflammation and clotting factors in the blood. For this reason, it can also sometimes be prescribed for other conditions, such as rheumatoid arthritis or to prevent cardiovascular events.

Similarly, sildenafil was originally developed for hypertension and to prevent heart disease but when it was used in practice a secondary effect to treat erectile dysfunction was discovered, which is it primary use on the market today.

Patient Safety

However, polypharmacology has the potential to cause problems when it is not used correctly, or insufficient information is known about the activity of the drug. This is primarily as a result of adverse effects that result from secondary drug targets.

For example, Lumiracoxib was removed from the drug market in Australia, due to concerns of the non-steroidal anti-inflammatory drug acting on the liver and leading to hepatic failure. Other drugs that have been the subject of similar concerns in respect to polypharmacology include rofecoxib and staurosporine.

The safe and effective use of medications with polypharmacological properties requires extensive data collation to ensure the best results. This process included computer models, synthetic chemistry, pharmacological testing and clinical trials before it can be implemented in widespread practice.

Scientific Research

At present, there is extensive research being carried out to gather data about polypharmacology and its place in the future of drug development. There are several databases resources that compile information about different medications, including:

  • Drug targets
  • Molecular pathways
  • Crystal structures
  • Binding experiments
  • Side effects
  • Biological and chemical properties
  • Disease relevance

Challenges

However, there remain some challenges in polypharmacology that limit their utility in drug development in the present and future.

Most prominently, the understanding of the pathways and mechanisms involved is not complete, and we do not comprehend the full effects of polypharmacological effect on the body at a molecular level. The technology and research currently available is often not sufficient to guarantee safety to patients that receive treatments with high confidence. Additionally, the costs to conduct necessary studies can be high.

Future of Drug Development

Polypharmacology certainly has the potential to play a larger role in the development of drugs in the future, although it is essential that appropriate care is taken to reap the benefits of multiple drug actions while minimizing the associated risks.

It is expected that in the near future, there will be more research in this area, particularly in the field of drug repurposing and extending the utility of drugs already approved for safety. This is likely to grow into the future, perhaps expanding to develop drugs initially to target unique pathways in the body.

References

Last Updated: Dec 13, 2015

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