Scientists develop tool to determine whether a drug will go rogue

5 Jan 2018

Image: Zolnierek/Shutterstock

Scientists have developed a tool that can identify potential ‘Jekyll and Hyde’ drugs capable of transforming a healing drug into a harmful version.

While pharmaceutical drugs are researched and manufactured with the intention of helping a patient, sometimes little-understood risks can lead to that drug turning on its master and inflicting serious harm on the patient.

In a paper published to the journal Angewandte Chemie, a team of UK researchers has revealed a tool that can test whether such a scenario is likely in a new drug, an area that has often been overlooked by the pharmaceutical industry.

The team believes that the new method could potentially lead to a significant reduction in the financial risk associated with drug development by identifying at-risk drug candidates early on in the production process, eventually leading to the efficient development of safe medication.

Right- and left-handed medication

The issue with medication comes from the fact that drug compounds known as enantiomers exist in either a ‘right-handed’ or ‘left-handed’ form, both of which have identical chemical compositions but which can’t create a superimposable image on one another.

Medication can contain both right- and left-handed versions of a compound but often, only one of a drug’s enantiomers is responsible for the desired physiologic effects, while the other enantiomer is less active, inactive or can sometimes produce adverse effects.

A famous example is thalidomide, which was sold in a number of countries over a period of four years, but caused numerous birth defects because while one enantiomer caused the intended sedative effects, the other created the birth defects.

While this crisis led to the banning of thalidomide and the ending of two enantiomer drugs, single enantiomer drugs can still create the flipped effect through a process known as racemisation, caused by the drug’s interaction with basic compounds in the water in the body.

Manufacture safer medication

So, to create this new test, the team simulated the chemical conditions of the human body and introduced a number of drugs to the system.

After monitoring their effects, the team was able to a create a simple mathematical model that could quickly predict the rate of racemisation in any drug compound, thereby indicating how safe and productive that drug would be if administered.

“While compounds are routinely tested to ensure they are inherently stable under physiological conditions, not much thought has been given as to how to prevent configurational instability at the design stage, using suitable predictive models,” said the study’s lead author, Dr Niek Buurma of Cardiff University.

“We believe that this risk assessment will make it possible to manufacture safer medication by helping the pharmaceutical industry to quickly spot medication that will fail during development, and focus their efforts on compounds that are more likely to work.”

Colm Gorey was a senior journalist with Silicon Republic